Heart Wall Research Articles

See-saw-like movement of right heart

Abstract Right atrial appendage aneurysm is a rare disease, which is usually diagnosed initially by transthoracic echocardiography and differentiated from pericardial effusion and other diseases. We described the motion pattern of the right heart wall in the case of a giant right atrial appendage aneurysm, which is different from the “pendulum-like” motion in the case of massive pericardial effusion. It merely affects the right heart wall, presenting a see-saw-like movement, while the left heart wall remains unaffected.

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.

Mutations that prevent phosphorylation of the BMP4 prodomain impair proteolytic maturation of homodimers leading to early lethality in mice.

Bone morphogenetic protein4 (BMP4) plays numerous roles during embryogenesis and can signal either as a homodimer, or as a more active BMP4/7 heterodimer. BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments. In humans, heterozygous mutations within the prodomain of BMP4 are associated with birth defects. We studied the effect of two of these mutations (p.S91C and p.E93G), which disrupt a conserved FAM20C phosphorylation motif, on ligand activity. We compared the activity of BMP4 homodimers or heterodimers generated from BMP4, BMP4S91C or BMP4E93G precursor proteins in Xenopus embryos and found that these mutations reduce the activity of BMP4 homodimers but not heterodimers. We generated Bmp4 S91C and Bmp4 E93G knock-in mice and found that Bmp4 S91C/S91C mice die by E11.5 and display reduced BMP activity in multiple tissues including the heart at E10.5. Most Bmp4 E93G/E93G mice die before weaning and Bmp4 -/E93G mutants die prenatally with reduced or absent eyes, heart and ventral body wall closure defects. Mouse embryonic fibroblasts (MEFs) isolated from Bmp4 S91C and Bmp4 E93G embryos show accumulation of BMP4 precursor protein, reduced levels of cleaved BMP ligand and reduced BMP activity relative to MEFs from wild type littermates. Because Bmp7 is not expressed in MEFs, the accumulation of unprocessed BMP4 precursor protein in mice carrying these mutations most likely reflects an inability to cleave BMP4 homodimers, leading to reduced levels of cleaved ligand and BMP activity in vivo. Our results suggest that phosphorylation of the BMP4 prodomain is required for proteolytic activation of BMP4 homodimers, but not heterodimers.

Histology slide is non-repeatable, non-reproducible and unreliable in estimating post-mortem heart wall thickness

ABSTRACT A routine measurement in heart examination is that of the heart wall thickness. This study investigated whether histology can be used to estimate heart wall thickness measured in a post-mortem examination, and therefore assess the utility of this method in the post-mortem report peer review process. This study compared 30 consecutive adult heart measurements (left and right free wall thickness and interventricular wall thickness). It showed that heart wall thickness measurements on histology slides were non-repeatable, non-reproducible, and unreliable, with overall poor to moderate intraclass correlation coefficient (<0.60, p < 0.05). The 95% confidence interval in the difference between histology and post-mortem examination was 1–3.5 mm for left ventricle and interventricular wall thickness, and −1–0.5 mm for the right ventricle. This study showed limited utility in using histology in estimating heart wall thickness. However, in instances where histology was the only modality available to estimate heart wall, marking where the measurements were taken, citing the confidence intervals, and noting the limitations thereof is recommended.

Simulating cardiac fluid dynamics in the human heart.

Cardiac fluid dynamics fundamentally involves interactions between complex blood flows and the structural deformations of the muscular heart walls and the thin valve leaflets. There has been longstanding scientific, engineering, and medical interest in creating mathematical models of the heart that capture, explain, and predict these fluid-structure interactions (FSIs). However, existing computational models that account for interactions among the blood, the actively contracting myocardium, and the valves are limited in their abilities to predict valve performance, capture fine-scale flow features, or use realistic descriptions of tissue biomechanics. Here we introduce and benchmark a comprehensive mathematical model of cardiac FSI in the human heart. A unique feature of our model is that it incorporates biomechanically detailed descriptions of all major cardiac structures that are calibrated using tensile tests of human tissue specimens to reflect the heart's microstructure. Further, it is the first FSI model of the heart that provides anatomically and physiologically detailed representations of all four cardiac valves. We demonstrate that this integrative model generates physiologic dynamics, including realistic pressure-volume loops that automatically capture isovolumetric contraction and relaxation, and that its responses to changes in loading conditions are consistent with the Frank-Starling mechanism. These complex relationships emerge intrinsically from interactions within our comprehensive description of cardiac physiology. Such models can serve as tools for predicting the impacts of medical interventions. They also can provide platforms for mechanistic studies of cardiac pathophysiology and dysfunction, including congenital defects, cardiomyopathies, and heart failure, that are difficult or impossible to perform in patients.

MANIFESTATIONS OF ENDOGENOUS INTOXICATION SYNDROME DEPENDING ON ITS ACTIVITY ACCORDING THE LEVEL OF MEDIUM-MASS MOLECULES

Substances of endogenous intoxication syndrome (EIS), which belong to medium-mass molecules (MMM), have cardiovascular toxicity; their content is increased in conditions of chronic heart failure. However, the influence of EIS activity has been studied not enough, which determined the relevance and expediency of our study.Aim. In order to compare the laboratory-instrumental features of the course of metabolically associated liver steatosis (LS) under the conditions of pronounced and insignificant activity of EIS, 19 patients (10 men, 9 women; average age 61,8 years) with coronary artery disease (CAD), atherosclerotic cardiosclerosis, HF of I-II FC and sonographically diagnosed LS were examined. Depending on the level of MMM, patients were divided into two groups with pronounced EIS (MMM &gt;0,6 units) and moderate activity (MMM &lt;0,6 units), which were identical in gender and age composition, hemodynamic indicators, body mass index and area body surface. Photometric determination of MMM total and at wave lengths of 238, 254, 266, 282 nm in blood and urine was carried out; determination of blood L-arginine and urine nitrites, leptin were provided; aromaticity coefficient 238/282, hepato-steatosis index, AST/platelet ratio, nuclear intoxication index (NII), the ratio of lymphocytes and neutrophils to monocytes were calculated. All results were calculated statistically, the level of significance was taken as p&lt;0.05.The results. Among the examined patients, 36.8% had high EIS activity (grades 2-3), and in 63.2% it was moderate (grade 1). Patients with pronounced EIS activity were characterized by hypoalbuminemia, dyslipidemia, low leptin content and higher arginine level, peripheral blood lymphopenia, and relative thinning of the heart walls. The content of MMM254,266,282 in blood was correlated with the size of the left ventricle in diastole, MMM266,282 in urine - with total cholesterol, low and very low density its particles and triglycerides, the aromaticity coefficient - with urinary nitrites. Integral hematological NII was directly proportional to diastolic pressure, and the lymphocyte/monocyte ratio - to systolic pressure. The ratio of neutrophils to monocytes and AST/platelets were correlated with the content of total bilirubin; and the hepato-steatosis index - with high-density lipoproteins and the coefficient of atherogenicity.Conclusion. Patients with concomitant metabolic-associated steatosis of the liver and a high level of EIS were characterized by metabolic disorders. Specific indicators of EIS correlated with parameters of lipid metabolism and hemodynamics.

Removal of leads broken during extraction: A comparison of different approaches and tools.

Extraction of a broken lead fragment (BLF) has received scant attention in the literature. Retrospective analysis was to compare the effectiveness of different approaches and tools used for BLF removal during 127 procedures. A superior approach was the most popular (75.6%), femoral (15.7%) and combined (8.7%) approaches were the least common. Of 127 BLFs 78 (61.4%) were removed in their entirety and BLF length was significantly reduced to less than 4 cm in 21 (16.5%) or lead tip in 12 (9.4%) cases. The best results were achieved when BLFs were longer (>4 cm) (62/93 66.7% of longer BLFs), either in the case of BLFs free-floating in vascular bed including pulmonary circulation (68.4% of them) but not in cases of short BLFs (20.0% of short BLFs). Complete procedural success was achieved in 57.5% of procedures, the lead tip retained in the heart wall in 12 cases (9.4%) and short BLFs were found in 26.0%, whereas BLFs >4 cm were left in place in four cases (3.1%) of procedures only. There was no relationship between approach in lead remnant removal and long-term mortality. (1) Effectiveness of fractured lead removal is satisfactory: entire BLFs were removed in 61.4% (total procedural success-57.5%, was lower because five major complications occurred) and BLF length was significantly reduced in 26.0%. (2) Among the broken leads, leads with a long stay in the patient (16.3 years on average), passive leads (97.6%) and pacemaker leads 92.1% are significantly more common, but not ICD leads (only 7.9% of lead fractures) compared to TLE without lead fractures. (3) Broken lead removal (superior approach) using a CS access sheath as a "subclavian workstation" for continuation of dilatation with conventional tools deserves attention. (4) Lead fracture management should become an integral part of training in transvenous lead extraction.

Cardiotoxicity of Cadmium and Its Effects on Heart Efficiency During Early and Late Chick Embryogenesis

Cadmium (Cd) is a dangerous heavy metal that is non-degradable in the environment. Many organs can accumulate Cd and adversely affect organ function and health. Cd is considered as a teratogenic and embryotoxic agent. This study aims to evaluate the teratogenicity of Cd at concentrations lesser than the permissible and its effects on the heart during chick embryogenesis. Fertilized eggs of the chick Gallus domesticus were divided into; control, saline injected and four experimental groups injected with single doses of 5, 25, 50 or 75 µM of CdCl2. Histological observations of the heart before hatching and the cardiomyocytes after hatching were recorded. Morphometric measurements of heart chambers were achieved at 3, 4 and 6 days of incubation. Electrocardiograph and respiratory rate were recorded at tenth day. Different cardiac problems had been brought on by Cd. In comparison to controls, the heart looked much larger, and in certain cases, growth retardation was seen. Degeneration in heart walls and malformations of dorsal aorta were noticed. Morphometrically, the width and wall thickness of heart chambers showed significant changes. Heart beats and respiratory rate significantly decreased compared to control. The cardiotoxic effect of Cd on heart compartments structure and function was dose dependent. One of Cd toxicity is its ability to induce cellular oxidative stress. The heart in particular is sensitive to oxidative stress. Cardiac oxidative stress might intensify heart failure and promote disease progression. Calcium is one of the components that is needed for normal heart work. Cd might interfere with calcium metabolism by removing it from the body.

Isoproterenol induced cardiac hypertrophy: A comparison of three doses and two delivery methods in C57BL/6J mice.

Heart Failure (HF) continues to be a complex public health issue with increasing world population prevalence. Although overall mortality has decreased for HF and hypertrophic cardiomyopathy (HCM), a precursor for HF, their prevalence continues to increase annually. Because the etiology of HF and HCM is heterogeneous, it has been difficult to identify novel therapies to combat these diseases. Isoproterenol (ISP), a non-selective β-adrenoreceptor agonist, is commonly used to induce cardiotoxicity and cause acute and chronic HCM and HF in mice. However, the variability in dose and duration of ISP treatment used in studies has made it difficult to determine the optimal combination of ISP dose and delivery method to develop a reliable ISP-induced mouse model for disease. Here we examined cardiac effects induced by ISP via subcutaneous (SQ) and SQ-minipump (SMP) infusions across 3 doses (2, 4, and 10mg/kg/day) over 2 weeks to determine whether SQ and SMP ISP delivery induced comparable disease severity in C57BL/6J mice. To assess disease, we measured body and heart weight, surface electrocardiogram (ECG), and echocardiography recordings. We found all 3 ISP doses comparably increase heart weight, but these increases are more pronounced when ISP was administered via SMP. We also found that the combination of ISP treatment and delivery method induces contrasting heart rate, RR interval, and R and S amplitudes that may place SMP treated mice at higher risk for sustained disease burden. Mice treated via SMP also had increased heart wall thickness and LV Mass, but mice treated via SQ showed greater increase in gene markers for hypertrophy and fibrosis. Overall, these data suggest that at 2 weeks, mice treated with 2, 4, or 10mg/kg/day ISP via SQ and SMP routes cause similar pathological heart phenotypes but highlight the importance of drug delivery method to induce differing disease pathways.

PREVALENCE AND MANAGEMENT OF MALNUTRITION IN CHILDREN WITH CONGENITAL HEART DISEASE : A COMPREHENSIVE SYSTEMATIC REVIEW

Background: Congenital heart disease is a congenital abnormality that affects the structure of the heart walls and vessels. Malnutrition has a significant impact on the likelihood of infection in children with congenital heart disease, which leads to poor treatment outcomes. The aim: The aim of this study to show about prevalence and management of malnutrition in children with congenital heart disease. Methods: By the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. This search approach, publications that came out between 2014 and 2024 were taken into account. Several different online reference sources, like Pubmed, SagePub, and Sciencedirect were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done. Result: Five publications were found to be directly related to our ongoing systematic examination after a rigorous three-level screening approach. Subsequently, a comprehensive analysis of the complete text was conducted, and additional scrutiny was given to these articles. Conclusion: Nutrition is crucial in the treatment of chronic illness. It’s one of the most important factors affecting patients’ recovery after surgery and lowering the risk of infection in children with congenital heart disease.

Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells.

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+ T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.

Cardiotoxicity of the diamide insecticide chlorantraniliprole in the intact heart and in isolated cardiomyocytes from the honey bee

In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca2+ release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1–10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca2+ channels responsible for the cardiac action potentials depolarization phase. Two types of Ca2+ currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca2+ currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.

Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab: a phase 1 clinical study in Japanese patients with renal cell carcinoma (Zirdac-JP).

PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. Eligible adult patients received 37MBq (± 10%; 10mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72h and Day 5±2d after administration. [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean±standard deviation) (1.365±0.245mGy/MBq), kidney (1.126±0.190mGy/MBq), heart wall (1.096±0.232mGy/MBq), and spleen (1.072±0.466mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

Unveiling MiRNA-124 as a biomarker in hypertrophic cardiomyopathy: An innovative approach using machine learning and intelligent data analysis

BackgroundHypertrophic cardiomyopathy (HCM) is a widespread hereditary cardiac pathology characterized by thickened heart walls and rearrangement of cardiomyocytes. Despite extensive research, the mechanisms underlying HCM development remain poorly understood, impeding the development of effective therapeutic and diagnostic strategies. Recent studies have suggested a polygenic nature of HCM development alongside monogenic forms. Transcriptomic profiling is a valuable tool for investigating such diseases. In this study, we propose a novel approach to study regulatory microRNAs (miRNAs) in the context of HCM, utilizing state-of-the-art data analysis tools. Methods and resultsOur method involves applying the Monte Carlo simulation and machine learning algorithm to transcriptomic data to generate high-capacity classifiers for HCM. From these classifiers, we extract key genes crucial for their performance, resulting in the identification of 16 key genes. Subsequently, we narrow down the pool of miRNAs by selecting those that may target the greatest number of key genes within the best models. We particularly focused on miR-124-3p, which we validated to have an association with HCM on an independent dataset. Subsequent investigation of its function revealed involvement of miR-124-3p in the RhoA signaling pathway. ConclusionsIn this study we propose a new approach to analyze transcriptomic data to search for microRNAs associated with a disease. Using this approach for transcriptomic profiling data of patients with HCM, we identified miR-124-3p as a potential regulator of the RhoA signaling pathway in the pathogenesis of HCM.

Lead break during extraction - predisposing factors and impact on procedure complexity and outcome on the basis of analysis of 3825 procedures

Abstract Background There are no reports describing lead break (LB) during transvenous lead extraction (TLE). Our aim was to compare the effectiveness of different approaches and tools used for LB removal during 127 procedures. Methods Retrospective analysis of 3825 consecutive TLEs using mechanical sheaths. Results Fracture of the lead defined as LB with a long lead fragment (LF) occurred in 2.48%, LB with a short LF in 1.20%, LB with the tip of the lead in 1.78% and LB with loss of a free-floating LF in 0.57% of cases. In total, extractions with LB occurred in 6.04%. In cases in which lead remnant was equivalent to a lead fragment (more than the lead tip only) there was a 50.31% chance of removing the LF in its entirety and an 18.41% chance of significantly reducing its length (to less than 4 cm). Risk factors for LB are similar to those for major complications and increased procedure complexity: long lead dwell time [OR=1.018], higher LV ejection fraction, multiple previous CIED-related procedures and extraction of passive fixation leads. A superior approach was the most popular (75.59%), femoral (15.75%) and combined (8.66%) approaches were the least common. Broken lead fragments (BLFs) were removed in their entirety in 63.78% and BLF length was significantly reduced (to less than 4 cm) in 24.41%. The best results were achieved when BLFs were longer (&amp;gt;4 cm) (66.67%), either free-floating or in the pulmonary circulation (68.42%) but not in cases of short BLFs (20.0%). Complete procedural success was achieved in 70.87% of procedures, the lead tip retained in the heart wall and short BLFs were found in 25.98%, whereas BLFs &amp;gt; 4 cm were left in place in 3.15% of procedures only. There was no relationship between approach in lead remnant removal and long-term mortality. All forms of LB were associated with increased procedure complexity and major complications (9.96% and 1.53%). There was no procedure-related death among such patients and LB did not affect survival after TLE. Conclusions 1. LB during TLE occurs in 6.04% of procedures and it increases procedure complexity and risk of major complications. Thus, the possibility of LB should be taken into account when planning lead extraction strategy and training. 2. Effectiveness of fractured lead removal is satisfactory. 3.Risk factors for lead fracture are implant duration (16.27 years on average), ventricular leads (71.65%), passive fixation leads (97.63%) and pacemaker leads (92.13%), but not ICD leads (only 7.87% of lead fractures). 4. Broken lead removal using a coronary sinus access sheath as a "subclavian workstation" for continuation of dilatation with conventional tools deserves attention.

Computed tomography as a predictive tool for ventricular tachycardia

Abstract Background Sudden cardiac death is the main cause of mortality worldwide. It is often linked with ventricular tachycardia (VT). To prevent VT, high-risk patients are typically equipped with intracardiac defibrillators (ICDs). Currently, left ventricular ejection fraction (LVEF) is the standard for determining a patient's risk level. Objective We hypothesized that the use of imaging software analyzing cardiac CT-scans could enhance the detection of patients with an increased risk of VT. Methods and Results In this study, 132 patients with ischemic cardiomyopathy (average age 66.2±11.4 years, with an average LVEF of 36.6±10.3%), all with implanted cardiac devices, underwent CT scans. We developed software to automatically analyze the heart's wall tissue thickness, cardiac fat, and calcification levels (Figure.1.A). A viable cardiac wall thickness of less than 3mm typically indicates a ventricular wall predominantly composed of scar tissue with minimal viable tissue remaining. In contrast, a viable wall thickness of less than 5mm includes regions with more viable tissue and therfore represents the total scar. Over an average follow-up of 6.6 years (79.8 ± 30.5 months) via live telemedicine, we observed that patients with VT had a significant difference in wall thickness ratio (3mm/5mm; no VT 0.31±0.18 vs, VT 0.44±0.18, p&amp;lt;0.01)) and higher calcification (0.10±0.38ml vs. 0.47±1.57ml, p=0.039). The amount of cardiac fat did not significantly differ between the no VT and VT groups (1.14±1.38ml vs.1.21±1.01ml, p=0.771). Logistic regression determined a critical cutoff for wall thickness at a ratio of 0.3 for 3mm and 5mm thickness. Kaplan Meyer analysis contrasted this wall thickness ratio of 0.3 (figure.1.B) against the established LVEF threshold of 35% (figure.1.C) for predicting VT-free survival, revealing a notable disparity favoring wall thickness ratio (p&amp;lt;0.01) over LVEF (p=0.77). Conclusions The findings suggest that a higher proportion of regions of thin viable tissue or dense scar in the total scar is a more effective predictor of VT-free survival than LVEF, potentially improving the identification of patients at risk for sudden cardiac death.Figure. 1

Investigation of the Frequency of IL27 Gene -964 A&gt;G Polymorphism (rs153109) in Infants with a History of Heart Wall Defects in Yazd

Background: Congenital Heart Disease (CHD) is one of the leading causes of infant mortality with some problems in the heart's structure at birth. One of the most common congenital heart diseases is the septal defect, in which there is a hole in the wall (septum). Although the etiology of CHD is mainly unknown, numerous studies have suggested both genetic and environmental factors contribute to the development of this disease. This study aims to investigate the frequency of -964 A&gt;G polymorphism (rs153109) in the IL27 gene in infants with CHD in Yazd province, Iran. Methods: The study included 30 infants with CHD. We genotyped the IL27 polymorphism by using the PCR- Sequencing technique. Results: Data revealed that the frequencies of AA, AG, and GG among the population of Yazd province were 40%, 40%, and 20%, respectively. The frequency of A and G alleles were 60% and 40%, respectively. Conclusion: The higher frequency of the A allele in patients with CHD compared to the G allele suggests that the A allele may increase atrial septal defect and ventricular septal defect susceptibility in Yazd province. It is recommended that the presence of the A allele and AG genotype be used as a predictor for the development of septal defects.

Bromuconazole exposure induces cardiac dysfunction by upregulating the expression LEF1

With the wide application of bromuconazole (BRO), a kind of triazole fungicide, the environmental problems caused by BRO have been paid more and more attention. In this study, adult male zebrafish were exposed to environmental related concentration and the maximum non-lethal concentration for zebrafish larvae (0,50 ng/L and 7.5 mg/L) for 7 days, respectively. Zebrafish exposed to BRO exhibited a significant reduction in body length and an increase in fatness index, indicating adverse physiological changes. Notably, the exposed zebrafish showed enlarged heart ventricular volumes and thinner heart walls. Transcriptome analysis of heart samples showed that BRO exposure mainly affected pathways related to cardiac energy metabolism. In addition, the amount of ATP in the heart tissue was correspondingly reduced, and the expression levels of genes related to controlling ion balance and myosin synthesis in the heart were also altered. The study extended its findings to the rat cardiomyocytes (H9C2), where similar cardiotoxic effects including changes in transcription of genes related to energy metabolism and heart function were also observed, suggesting a potential universal mechanism of BRO-induced cardiotoxicity. In a doxorubicin (DOX) induced larval zebrafish heart failure model, the expression of lymphoid enhancer-binding factor 1(LEF1), a key gene in the Wnt/β-catenin signaling pathway, was significantly increased in larval zebrafish and adult fish heart tissues and cardiomyocytes, suggesting that LEF1 might play an important role in BRO-induced cardiotoxicity. Taken together, BRO exposure could interfere with cardiac function and metabolic capacity by abnormal activation the expression of LEF1. The study emphasized the urgent need for monitoring and regulating BRO due to its harmful effects on the hearts of aquatic organisms.

Total-body imaging of mu-opioid receptors with [11C]carfentanil in non-human primates

PurposeMu-opioid receptors (MORs) are widely expressed in the central nervous system (CNS), peripheral organs, and immune system. This study measured the whole body distribution of MORs in rhesus macaques using the MOR selective radioligand [11C]carfentanil ([11C]CFN) on the PennPET Explorer. Both baseline and blocking studies were conducted using either naloxone or GSK1521498 to measure the effect of the antagonists on MOR binding in both CNS and peripheral organs.MethodsThe PennPET Explorer was used for MOR total-body PET imaging in four rhesus macaques using [11C]CFN under baseline, naloxone pretreatment, and naloxone or GSK1521498 displacement conditions. Logan distribution volume ratio (DVR) was calculated by using a reference model to quantitate brain regions, and the standard uptake value ratios (SUVRs) were calculated for peripheral organs. The percent receptor occupancy (%RO) was calculated to establish the blocking effect of 0.14 mg/kg naloxone or GSK1521498.ResultsThe %RO in MOR-abundant brain regions was 75–90% for naloxone and 72–84% for GSK1521498 in blocking studies. A higher than 90% of %RO were observed in cervical spinal cord for both naloxone and GSK1521498. It took approximately 4–6 min for naloxone or GSK1521498 to distribute to CNS and displace [11C]CFN from the MOR. A smaller effect was observed in heart wall in the naloxone and GSK1521498 blocking studies.Conclusion[11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose.

Attention LSTM U-Net model for Drosophila melanogaster heart tube segmentation in optical coherence microscopy images.

Optical coherence microscopy (OCM) imaging of the Drosophila melanogaster (fruit fly) heart tube has enabled the non-invasive characterization of fly heart physiology in vivo. OCM generates large volumes of data, making it necessary to automate image analysis. Deep-learning-based neural network models have been developed to improve the efficiency of fly heart image segmentation. However, image artifacts caused by sample motion or reflections reduce the accuracy of the analysis. To improve the precision and efficiency of image data analysis, we developed an Attention LSTM U-Net model (FlyNet3.0), which incorporates an attention learning mechanism to track the beating fly heart in OCM images. The new model has improved the intersection over union (IOU) compared to FlyNet2.0 + with reflection artifacts from 86% to 89% and with movement from 81% to 89%. We also extended the capabilities of OCM analysis through the introduction of an automated, in vivo heart wall thickness measurement method, which has been validated on a Drosophila model of cardiac hypertrophy. This work will enable the comprehensive, non-invasive characterization of fly heart physiology in a high-throughput manner.