Wall Of Ventricle Research Articles

#2359 Kinetic modifications in cardiac remodeling in a rat model of CKD

Abstract Background and Aims The bi-directional relationship between the kidneys and heart leads to different forms of cardiorenal syndrome (CRS) in which acute or chronic dysfunction in one organ affects the other. CRS type 4 is characterized by chronic kidney disease leading to the impairment of cardiac function through diastolic dysfunction and cardiac remodeling, such as fibrosis and hypertrophy. The progression of CRS type 4 occurs dynamically thus identifying key changes could prove beneficial for treatment and prediction of outcome for the patients. This present study assessed the impact on heart remodeling and function after 12 and 24 weeks of chronic kidney disease in rats undergoing subtotal nephrectomy. Method Twelve-week-old Sprague Dawley male rats either underwent 5/6 nephrectomy (SNX) or Sham operated and were sacrificed at 12 or 24 weeks after kidney infarction. Serum creatine levels were assessed using the epoc® Blood Analysis System. Before sacrifice, a catheter was inserted into the right carotid artery for systolic arterial pressure (SAP) measurement. Echocardiography (VisualSonics/Fujifilm) was performed under isoflurane anesthesia. To determine the diastolic function of the heart, mitral flow was assessed and recorded using a pulse-wave doppler. The peak early filling (E wave)-to-late diastolic filling (A wave) ratio (E/A) as well as E deceleration time was used to determine diastolic function. Left Ventricle posterior wall thickness (LVPW_S) was measured during end-systole and end-diastole. Image analyses were performed using VisualSonics Vevolab 3.1.0 software. Fibrosis of the kidney and left ventricle was determined through Sirius Red histology staining. The mRNA expression levels of FGF23 and GDF-15 were measured through qPCR. Unpaired T-test, Non-parametric, or One-way ANOVA were applied, and log transformation was performed when applicable. Statistical Analysis was performed using GraphPad Prism 8 software. Results The plasma creatinine dosage confirmed the renal insufficiency of the animals however, no changes were observed between 12 and 24 weeks of SNX (Table 1). Fibrosis in the kidney increased between 12 and 24 weeks of SNX as well as between their corresponding Sham (Table 1). Twenty-four weeks of SNX rats exhibited increased heart fibrosis in comparison to sham (Table 1). An increase in SAP was observed at 24 weeks of SNX in comparison to their Sham (Table 1). Cardiac remodeling between 12 and 24 weeks of SNX was observed through the increase in the left ventricle wall thickness (Table 1) (Fig. 1A). This was coupled with an increase in the expression of cardiac remodeling and protective-related genes FGF23 and GDF-15 (Fig. 1B,C). Diastolic function, as measured by E/A, remained unchanged in the model at both ages (Table 1). E deceleration time decreased at 24 weeks of SNX compared to their Sham (Table 1). Conclusion These preliminary results show a change in cardiac remodeling and function at 24 weeks of SNX compared to Sham. Between 12 and 24 weeks of SNX, changes in cardiac remodeling, namely hypertrophy of the posterior wall, can be observed. These changes were accompanied by an increase in FGF23 and GDF-15. As our model of cardio-renal syndrome has been characterized; we will turn our attention to the signaling involved in the establishment of cardiac fibrosis. This pre-clinical model will also make it possible to test new anti-fibrosis treatments.

THROW YOUR LEAD OVER THE OBSTACLE: A CHALLENGING CRT UPGRADING

Abstract High percentage of right ventricular pacing could lead to pacing induced cardiomyopathy in a non–negligible proportion of patients. Cardiac resynchronization therapy upgrading could represent an option to improve ventricular function, reducing heart failure hospitalizations. A 82 yo male was admitted to hospital with symptomatic heart failure. He had history of complete AV block treated with dual chamber pacemaker implantation five years earlier following coronary artery bypass graft surgery, bioprosthetic aortic valve replacement and septal myectomy. He had also history of cardiac arrest occurred in the context of acute coronary syndrome treated with PCI so that ICD implant was not considered at that time, and two more HF hospitalizations in previous years. Progressive LVEF decline was documented since PM impantation until last echo showed severe left ventricular dysfunction (EF 20% from baseline EF 60%). The ECG showed sinus rhythm and wide paced QRS (206 ms) with 100% pacing percentage. A CRT device upgrading was planned. Baseline venography initially showed pervious axillary–subclavian left axis, but unfortunately the guidewire encountered a complete occlusion before entering the superior vena cava. Nevertheless, dye contrast injection documented the presence of a proximal collateral branch (fig A) having a vertical course in the thorax and reaching the lateral wall of the left ventricle with an extrapericardic course then entering the right heart through inferior vena cava. Using a IM 5Fr sheath (usually used by interventional cardiologists to cannulate internal mammary artery) we could reach this branch, inserting a guidewire and finally advancing a quadripolar lead (Fig B–C) which reached the lateral left ventricular wall. LV capture was confirmed when pacing from the three proximal poles, while the distal one caused phrenic nerve capture. The quadripolar lead was connected to the LV port of a three chamber PM along with previous implanted leads thus obtaining biventricular pacing. QRS paced was 50 ms shorter than baseline. No peri–procedural complications occurred. Lead–related venous occlusion might represent an obstacle to CRT upgrade requiring high technical expertise. The presence of a complete venous occlusion might cause procedural failure, particularly in hospitals without surgical facility. In this case, the presence of a collateral branch reaching the lateral wall of the left ventricle allowed to successfully complete the CRT upgrade.

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY AND CARDIAC SARCOIDOSIS: THE GREY ZONE

Abstract Cardiac sarcoidosis (CS) is a rare multisystem disorder characterized by granulomatous infiltration of the myocardium, whose clinical manifestations can be extremely heterogeneus. We report the case of a 47–year–old man with a previous diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVD). In history he had a marked arrhythmic pattern with multiple episodes of sustained ventricular arrhythmias, biventricular disfunction (LVEF 37%, RVEF 32%) and extensive biventricular transmural late–gadolinium enhancement (greater than 50%) at cardiac RMN. At EKG epsilon wave mainly seen in precordial leads. In November 2022 he was implanted with bicameral defibrillator and in March 2023 he underwent ablation procedure for ventricular tachycardia with RF with endo–epicardial approach. In May 2023 he arrived at our Centre for acute decompensated heart failure. At restored hemodynamic stability, screening for the possible inclusion in transplant list was started. Right heart catheterization (RHC) showed low cardiac index with no pulmonary hypertension. Chest CT unexpectedly showed the presence of multiple micronodules with perilymphatic distribution with confluent appearance compatible with pulmonary sarcoidosis. In consideration of this result, the transplant program was temporarily postponed and investigations for possible cardiac involvement of an inflammatory nature were started. 18F–FDG PET–CT showed pulmonary, splenic, lymphonodal and especially cardiac uptake in the mid–distal segment of the lateral wall of the left ventricle and in the inferior–apical site suspicious for inflammatory pathology. Unfortunately, both lymphonodal and cardiac biopsies were inconclusive because of insufficient material. Nevertheless, the clinical scenario satisfied the Japanese criteria for possible CS; therefore, treatment with prednisone 1 mg/kg was started and a 18F–FDG PET–CT was planned after 3 months of steroid therapy. CS can disguise as a phenocopy of arrhythmogenic right ventricular cardiomyopathy because of several common characteristics, especially arrhythmic presentation. Due to these similarities, a careful overall evaluation of each patient with ARVD is mandatory as several transplant centers have reported cases of CS in explanted heart with a pretransplant misdiagnosis of ARVD or dilated cardiomiopathy. Performing a chest CT in all ARVD patients as part of transplant screening may be considered.

A RARE CASE OF INTERVENTRICULAR SEPTUM DUPLICATION

Abstract Case Report A 62–year–old man, history of hypertension. In 2015, there was suspicion of non–compaction cardiomyopathy, and he underwent cardiac MRI at another facility (report not available). The patient reported palpitations and dyspnea with exertion, leading to a follow–up visit. EKG showed sinus rhythm 90/min, nonspecific intraventricular conduction delay and isolated monomorphic ventricular ectopic beats. Echo revealed a mildly dilated left ventricle (end–diastolic volume 88 ml/m), systolic function at the lower limits of normal (EF 53%), and prominent muscular structures near the posterior interventricular septum (SIV), likely related to anomalies of the papillary muscles (prominent and possibly duplicated posterior–medial papillary muscle). There was apical trabecular protrusion, which did not meet the criteria for non–compaction (NC/C ratio in systole approximately 1), with no other significant findings. The cardiac MRI, performed to assess dilated cardiomyopathy, revealed a conspicuous structural abnormality in the septo–papillary region, located medio–apically and paraseptal–endocardial in the left ventricle. This anomaly lacked evident chordae tendineae with the mitral valve leaflets and exhibited synchronous systo–diastolic motion with the left ventricular wall, suggesting septal duplication. The septal thickness was slightly reduced, particularly in the medio–apical region. Additionally, there was hypertrabeculation of the posterior and lateral walls of the left ventricle, exceeding the threshold for non–compaction (NC/C ratio in end–diastole: 2.6 – normal range: <2.3). Left ventricular mass was normal (mass: 173.52 g; mass/body surface area (BSA): 86.58 g/m). Basal septum, medio–apical septum and medio–apical lateral wallshowed hypokinetic contractility. The left ventricle was dilated (end–diastolic diameter: 55.0 mm; end–systolic diameter: 45.3 mm – end–diastolic volume: 230 ml; stroke volume/BSA: 57.6 ml/m² – EF: 51%). Areas of late gadolinium enhancement (LGE) were observed in the anterior medio–basal septum and at the site of the described structural muscular anomaly, both displaying an intramural non–ischemic pattern. Conclusions The described findings suggest a picture of dilated cardiomyopathy and an associated structural septo–papillary anomaly of uncertain diagnostic interpretation (septum duplication with associated non–compacted myocardium? duplicated posterior–medial papillary muscle with associated non–compacted myocardium?).

Post COVID 19 Myocarditis: Clinical Case Series

Corona virus disease 2019 infection exhibits a tropism for the respiratory tract, however several cardiac damages have been reported, such as coronary disease, cardiac arrhythmias and myocarditis; this latter has become more frequent after the outbreak of the COVID-19 pandemic, and may be the only manifestation of COVID 19 infection, the diagnosis is not always obvious especially for focal myocarditis and can be misdiagnosed as an acute coronary syndrome in some patients. We reported five patients, admitted between June 2020 and January 2021, in our cardiology department for isolated acute focal myocarditis secondary to COVID 19 infection without respiratory or other damages, the diagnosis was not evident at first, but further investigations such as: electrocardiographic evolution, magnetic resonance imagery, coronary computed tomography angiography, and COVID 19 antibody testing, were in favor of the diagnosis of focal myocarditis secondary to COVID 19 infection. Cardiac magnetic resonance imaging showed, delayed contrast enhancement in the lateral wall of the left ventricle, for all five patients, so fibrosis is preferentially located in the lateral wall, and the outcome was favorable without hemodynamic or arrhythmic complications.

Influence of age on the incidence of acute complete atrioventricular block in right coronary artery infarction

Abstract Funding Acknowledgements None. Introduction Bezold-Jarisch is a cardioinhibitory reflex originating in cardiac vagal receptors, more concentrated in the inferoposterior wall of left ventricle, whose stimulation produces bradycardia and hypotension. The limited evidence suggests that vagal tone would predominate in younger individuals, whereas sympathetic tone would predominate in the elderly, resulting in a more striking Bezold-Jarisch reflex response among younger patients. Its maximum expression would be the occurrence of acute complete atrioventricular block (cAVB). Methods Observational, retrospective, single-centre analysis of consecutive patients hospitalised in the CCCU for STEACS with RCA or ADA as culprit artery (CA) between July 2011 and September 2022. We analysed the influence of age on the incidence of acute cAVB. Linear trend analysis and multivariate analysis were performed. Results A total of 723 patients with RCA as CA were included, with the baseline characteristics listed in Table1. Patients were divided into 4 groups: under 60 years (n=316 43.7%), 60-69 (n=223 30.8%), 70-79 (n=122 16.9%) and 80 or older (n=62 8.6%). The incidence of acute cAVB was 10.4%, 14.3%, 16.4% and 25.8% respectively (Fig1). A Cochran-Armitage analysis was performed, showing a significant linear trend between age and the incidence of acute cAVB (p=0.001). A multivariate analysis was performed using stepwise regression including age, sex, diabetes, hypertension, obesity, peripheral arterial disease, systolic blood pressure (SBP) at admission, renal failure, COPD, Killip-Kimbal (KK) score at admission and treatment with ticagrelor (for its described adenosine-like effect). Age (p=0.011), KK score (p<0.001) and lower SBP (p<0.001) were associated with a higher incidence of acute cAVB. Regarding the need for transient pacemaker, 6.2% of patients under 60, 7.7% aged 60-69, 10.1% aged 70-79, and 22.0% aged 80 and over required its implantation. As with cAVB, there was a significant linear trend between age and device implantation (p<0.001). Permanent pacemaker was implanted in only 6 patients. In-hospital mortality was significantly higher in patients with acute cAVB than all other patients with RCA infarction (7.9% vs 2.1%; p=0.001). Finally, as controls, acute cAVB data were analysed in patients with STEACS with ADA as CA (N=837). 366 patients (43.7%) were under 60 years, 204 (24.4%) 60-69, 155 (18.5%) 70-79 and 112 (13.4%) 80 or older. Only 10 patients presented with cAVB (1.2%), with no differences between those younger and older than 75 years (1.0% vs 2.3% respectively; p=0.13). Given the low incidence of cAVB in this group no further analysis was performed. Conclusion In RCA STEACS patients, there is a significant trend towards a higher incidence of acute cAVB with increasing age. These data suggest that older patients do not have a mitigated response to Bezold-Jarisch reflex. The inverse relationship between SBP and occurrence of cAVB supports the reflex nature of the mechanism.Table 1.Baseline characteristics.Fig 1.cAVB incidence among age groups.

Remodeling of Ventricular Catecholaminergic Axons Following Chronic Intermittent Hypoxia in Mice

Chronic intermittent hypoxia (CIH) is a widely employed model for sleep apnea. The imbalance of autonomic control may contribute to CIH-induced cardiovascular diseases. Previously, we demonstrated that CIH increases sympathetic innervation of the atria. In this study, we determined whether CIH remodels peripheral cardiac tyrosine hydroxylase (TH, a marker for sympathetic efferent axons) innervation in the whole ventricles. The two challenges here were: 1) labeling the entire TH-IR axon innervation in the full thickness (~500 μm) of whole flat-mount ventricles. 2) Quantifying the topographical distribution of TH-IR axons through the thick ventricular walls at the single axon/varicosity scale. In this study, C57BL/6J mice (male, 2 months old, n=7/group) were exposed to room air (RA, 21% O2) or CIH (alternating between 21% and 5.7% O2 every 6 minutes for 10 hours/day) for 8-10 weeks. We prepared flat-mounts of the whole ventricles and septum and processed them with immunohistochemical labeling for TH. Using the Zeiss M2 Imager, confocal microscope, Zeiss Arivis Vision 4D, and Neurolucida system, we traced and digitized the TH-IR axons. We found that: 1) In RA and CIH mice, several large TH-immunoreactive (TH-IR) bundles from the base area entered the ventricles and septum. These large bundles branched into numerous smaller bundles as they traveled downward toward the apex and finally developed into fine varicose axons and terminals in the epicardial and myocardial layers. 2) Using Vision 4D, we were able to accurately detect, trace, and digitize all TH-IR axons in the ventricle walls with high accuracy. 3) CIH increased overall TH-IR axon density and network complexity of the whole ventricles and septum. 3) Abnormal CIH TH-IR axon terminal structures were frequently seen. 4) We geometrically and precisely registered the tracing data into a scaffold map for presentation and comparison in 3D. Altogether, CIH increased sympathetic innervation of the heart which may contribute to the augmented sympathetic drive. Our success in mapping data in the 3D heart scaffold will establish a heart-brain connectome/atlas. Supported by NIH 1 U01 NS113867-01 NIH R15 1R15HL137143-01A1, 2R01HL137832-05 and Carl Zeiss. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

LONG-TERM PROGNOSIS OF THE DEVELOPMENT OF HEART FAILURE WITH LOW EJECTION FRACTION IN ACUTE CORONARY SYNDROME IN YOUNG AND MIDDLE-AGED PATIENTS WITH ARTERIAL HYPERTENSION

Objective: To determine the prognosis and dynamics of the development of heart failure with low ejection fraction (HFrEF) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) in young and middle-aged patients with arterial hypertension (AH) and type 2 diabetes mellitus (DM) Design and method: The study included 191 hypertensive patients aged 36-59 years with ACS after PCI. Group 1 - 76 patients with hypertension in combination with DM, group 2 - 115 patients with hypertension without DM. In 35 (46%) people of the 1st group and in 56 (48.7%) of the 2nd group, myocardial infarction (MI) of the anterior wall of the left ventricle (LV) was determined. The incidence of non-anterior MI (posterior and lateral walls) of the LV was 54% and 51.3% respectively. Patients in both groups were comparable. Observation was carried out for 12±1 months. Ejection fraction (EF), indices of LV end-systolic volume (LVESVI), LV end-diastolic volumes (LVEDVI), and index of impaired local contractility (ILCI) were determined over time. Results: On the first day after PCI, LVEF <40% (36%, 27-39%) in 14 of 76 (18.4%) in group 1; LVESVI - 43 ml/m2 (40-48 ml/m2); LVEDVI - 77 ml/m2 (67-87 ml/m2); ILCI 1.81 (1.63-2.0). After 12 months, LVEF decreased to 33% (28-39%) in 26 of 76 (34.2%) patients. The progression of HFrEF was indicated by an increase in initial LVESVI by 29-30% and LVEDVI by 23-35%. In group 2, on the first day after myocardial reperfusion in 8 out of 115 (7%) patients, LVEF was 38% (37 - 39%), LVESVI 44 ml/m2 (40-46 ml/m2), LVEDVI 69 ml/m2 m2 (64-76 ml/m2), ILCI 1.75 (1.13-1.88). After 12 months, HFrEF was detected in 10 of 115 (8.7%) patients with an increase in initial LVESVI values by 28%, LVEDVI by 31% and a decrease in LVEF to 36% (35-39%) (p = 0.0242). Conclusions: In young and middle-aged patients with hypertension in combination with DM, during the first 12 months after MI, in 34.2% of cases, there is a significant deterioration in the course of HFrEF, which requires an early decision on the timing of complete myocardial revascularization.

Epicardial Adipose Tissue and Left Ventricular Systolic Function in Rheumatoid Arthritis Assessed by Two-Dimensional Speckle Tracking Echocardiography.

Introduction Epicardial adipose tissue (EAT) is an emerging cardiovascular biomarker. Subclinical left ventricular (LV) systolic dysfunction is common in rheumatoid arthritis (RA). The aim of this study was to assess LV systolic function using two-dimensional speckle tracking echocardiography (2D-STE) and investigate its association with EAT in RA patients without clinical cardiovascular disease (CVD). Methods 60 RA patients without manifestations of CVD and 60 age- and gender-matched healthy controls have been recruited for the study. We assessed LV systolic function and EAT in all subjects using conventional echocardiography and 2D-STE. EAT was measured as the relative echo-free region between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole. Results Global longitudinal strain (GLS) was decreased and EAT was increased in the RA group compared to the control group. GLS was reduced as EAT increased in RA patients (r=-0.273, P=0.035). After adjusting for confounders, multivariate linear regression analysis revealed a weakened correlation between EAT and GLS.Age and disease activity scores28 were independent factors influencing GLS in RA. Conclusion RA patients have significantly thickened EAT compared with controls. 2D-STE can detect early LV myocardial systolic dysfunction in RA, as shown by lower GLS.Accumulation of EAT is associated with lower GLS, but older age and higher disease activity may play a greater role in LV myocardial systolic dysfunction in RA.

Sex Differences in Temporal Regulation of Piezo1 in Resiquimod Accelerated Systemic Lupus

Lupus disproportionally affects women (9:1), particularly women of color, but men with this disease often have more pronounced symptoms than their female counterparts. Individuals with lupus are anywhere from two to fifty times as likely to experience a cardiovascular (CV) event than the rest of the population. Though such complications are widely known, the mechanisms these disease processes are unknown. One well established pathogenesis of many CV diseases stems from an alteration of mechanical forces. The cation channel, Piezo1, is a mechanosensitive channel and is known to play a critical role in CV diseases like heart failure. Therefore, we hypothesized that inducing lupus-associated cardiac pathology in a lupus-prone mouse model would increase the expression of Piezo1. To investigate this, lupus-prone female and male B6.Nba2 mice aged 10-14 weeks were subjected to Resiquimod (R848; a TLR7/8 agonist;100μg/30μl) treatment or acetone vehicle twice a week for four weeks. Echocardiograms were performed every four weeks. Mice were sacrificed and their tissues harvested at 4- and 16-weeks after the start of R848 treatment. Piezo1 levels were subsequently analyzed in the heart by real time quantitative polymerase chain reaction (RTqPCR), immunoblot, and immunofluorescent staining. By echocardiography, female mice treated with R848 showed an increase in left ventricle (LV) wall thickness was seen at four weeks, followed by an increase in internal diameters over the following 12 weeks, culminating in cardiac dysfunction by 16 weeks via significantly decreased ejection fraction (EF; p<0.05) Interestingly, males showed no such cardiac dysfunction at any timepoint. By RTqPCR, female Piezo1 levels were higher overall than their male counterparts (p<0.05). Cardiac Piezo1 gene expression at 4 weeks was shown to be decreased in the R848-treated groups of both sexes. At 16 weeks, this trend was reversed in both male and female mice, showing R848-treatment induced an an upregulation of cardiac Piezo1 compared to each sex’s respective vehicle controls. Interestingly, while Piezo1 protein expression followed the same 4-week trend of downregulation in R848-treated mice regardless of sex, protein expression in the female R848-treated heart continued in a trending increase at the 16-week timepoint, while the male R848 heart showed unchanged. We found that this increase in cardiac Piezo1 in female, R848-treated is significantly correlated with higher left ventricular internal diameters (both LV-EDV (p<0.05) and -ESV (p<0.01)). This data demonstrates a sex difference phenotype in lupus-associated murine cardiac dysfunction, potentially through a Piezo1-mediated pathway. Further investigation is warranted to elucidate the Piezo1-dependent mechanisms involved in lupus-associated cardiovascular disease. Veterans Affairs Biomedical Laboratory Research & Development Career Development Award (CDA-2) 1IK2BX005605-01 to J.P.V.B, Medical University of South Carolina College of Medicine Program Project Grant to and J.P.V.B., and Medical University of South Carolina Core Centers for Clinical Research Project Award P30AR072582 to M.A.C and J.P.V.B. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Formation and development of lamellar histoarchitecture of the ventricular myocardium of chick embryos

Background. The existence of several models of the myolamellar structure of the ventricular myocardium, which currently has a number of contradictory provisions, reflects the need for a reasonable integration of the results of different methods. Under these circumstances, the study of those ontogenetic mechanisms that are responsible for the formation and development of the myolamellar architecture of the myocardium is of great interest. The purpose of the study is to determine the ontogenetic transformations of the embryonic chicken heart that ensure the formation and development of the myolamellar structure of the ventricular myocardium. Methods. The work examined the embryos of Cobb500 cross chickens from the beginning of the 10th day to the 21st day of incubation. The lamellar organization of the ventricular myocardium was studied using light and transmission electron microscopy. Results. Starting from the 36th stage according to NN (the beginning of the 10th day of incubation), the active development of the stromal component was observed in the heart of chicken embryos, which led to the division of the tissue of the compact ventricular myocardium into groups of muscle fibers in the form of narrow elongated flat plates containing thicker than 3 to 5 rows of cardiomyocytes. At the 41st and 43rd stages of development, active development of the intercellular matrix and division of the myocardium mass into muscle plates continued as part of the compact ventricular myocardium. The intercellular spaces within the plates narrowed, and between the myolamellae, the perimysium accumulated elements of the microcirculatory bed, functionally active fibroblasts, a large amount of amorphous substance, and bundles of formed collagen fibers. At the final stages of embryogenesis, the muscle plates of the left ventricle acquired a pronounced spiral orientation with a gradual displacement of the long axis of the muscle fibers in the direction from the apex of the ventricle to its base. In the wall of the right ventricle, the location of the myolamella acquired a transverse oblique-circular orientation. Conclusion. A comparison of the structure and geometry of the myolamella made it possible to reveal that starting from the 38th stage of development in the left ventricle, the conditions for the translational-rotational mechanism of chamber contraction were formed and increased, in which the formation of the difference between the systolic and diastolic volumes of the left ventricle is ensured not only by the longitudinal apico-basal vector compression of the cavity, but also by mutual sliding of spirally oriented plates in the ventricular wall. In right ventricle, the contraction mechanism is based on the longitudinal-circular compression of the chamber in accordance with the oblique-circular orientation of the muscle fibers in the composition of the myolamella without displacement in the state of systole.

GPR30 selective agonist G-1 induced insulin resistance in ovariectomized mice on high fat diet and its mechanism

BackgroundPrevious in vivo and in vitro studies have demonstrated that estrogen receptor agonist G-1 regulates glucose and lipid metabolism. This study focused on the effects of G-1 on cardiometabolic syndrome and anti-obesity under a high fat diet (HFD). MethodsBilateral ovariectomized female mice were fed an HFD for 6 weeks, and treated them with G-1. A cardiomyocyte insulin resistance model was used to simulate the in vivo environment. The main outcome measures were blood glucose, body weight, and serum insulin levels to assess insulin resistance, while cardiac function and degree of fibrosis were assessed by cardiac ultrasound and pathological observations. We also examined the expression of p-AMPK, p-AKT, and GLUT4 in mice hearts and in vitro models to explore the mechanism by which G-1 regulates insulin signaling. ResultsG-1 reduced body weight in mice on an HFD, but simultaneously increased blood glucose and promoted insulin resistance, resulting in myocardial damage. This damage included disordered cardiomyocytes, massive accumulation of glycogen, extensive fibrosis of the heart, and thickening of the front and rear walls of the left ventricle. At the molecular level, G-1 enhances gluconeogenesis and promotes glucose production by increasing the activity of pyruvate carboxylase (PC) while inhibiting GLUT4 translocation via the AMPK/TBC1D1 pathway, thereby limiting glucose uptake. ConclusionDespite G-1's the potential efficacy in weight reduction, the concomitant induction of insulin resistance and cardiac impairment in conjunction with an HFD raises significant concerns. Therefore, comprehensive studies of its safety profile and effects under specific conditions are essential prior to clinical use.

Massive Myocardial Calcification: A Rare Autopsy Finding

Introduction: Myocardial calcification is rare and occur by two mechanisms- dystrophic and metastatic. It can present with variable clinical manifestations like congestive heart failure, cardiomyopathy, arrhythmia and sudden cardiac death. Case Report: Post mortem viscera of a 50 year old male was received in the department of pathology with alleged history of burns, who died after two weeks of hospital treatment. There was no past history or investigation available in the post mortem papers. Whole heart, pieces of brain, both lungs, liver, spleen and both kidneys were received. On gross examination no abnormality was observed in any of these viscera. Microscopic examination revealed extensive calcification in anterior, lateral & posterior walls of left ventricle of the heart. Sections from kidney showed features of chronic tubulointerstitial nephritis. Conclusion: Myocardial calcification is rare and mostly diagnosed incidentally or on autopsy. Extensive sampling of heart and other viscera might help in finding the etiology in such rare cases of massive calcification in myocardium . Antemortem diagnosis can be made with computed tomography (CT) scan and endomyocardial biopsy.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report

BackgroundTuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported.Case presentationAn 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5–6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging.ConclusionOver half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

The levels of visfatin and toll-like receptors in arterial hypertension and type 2 diabetes mellitus

Hypertension and type 2 diabetes mellitus (DM) remain widespread diseases that are becoming more prevalent. The role of visfatin and toll-like receptor (TLR) molecules in the pathogenesis of these diseases requires further research. Our aim was to study changes in visfatin and TLR levels in patients with hypertension and type 2 diabetes. Fifty-one patients were examined and divided into two groups: group 1 included 27 patients with hypertension and group 2 included 24 people with hypertension and type 2 DM. The control group included 18 practically healthy people. All individuals underwent general blood test, coagulogram, biochemical blood test, enzyme immunoassay to determine the level of visfatin and TLR in the blood serum and echocardiography. Hypertrophy of the walls of the left ventricle (LV) was observed in patients of two observed groups. The most common type of LV geometry was concentric hypertrophy (41.2%). The level of visfatin was significantly higher in patients of group 1, while in patients of group 2 it was decreased (P ˂ 0.05) and the level of TLR was increased (P ˂ 0.05). The elevated level of TLR in the serum of patients with hypertension can be considered a factor of low-grade inflammation, especially in combination with type 2 DM. The increase in the concentration of visfatin in hypertension serves as a more sensitive marker compared to TLR regarding the risk of developing comorbid cardiovascular pathology. The therapeutic treatments of patients with type 2 DM cause a reduction in the concentration of visfatin induced by hypertension. Keywords: hypertension, toll-like receptors, type 2 diabetes mellitus, visfatin

Choosing the Adaptive Cardiac Phase for Assessing Cardiac Dimensions Using Cardiac Computed Tomography for Heart Disease

Cardiac chamber dimensions and left ventricle (LV) wall thickness change with the cardiac cycle, in which researchers have set different time points for systole and diastole. This study aimed to provide characteristics of normal heart and choose the correct cardiac cycle to measure maximum cardiac parameters for cardiovascular disease. The parameters of left atrium (LA), LV, right atrium (RA), and right ventricle (RV), as well as the wall thickness of LV, were measured in different cardiac phases using cardiac computed tomography (CT). Then, their differences in different phases and the correlation between these parameters and traditional risk factors were analyzed. In addition, receiver operator characteristic curve (ROC) analyses was performed to estimate LA enlargement. The dimensions of LA and RA as well as the wall thickness of LV reached the maximum at the phase of 35% – 45%, while the dimensions of LV and RV reached the maximum at 95% – 5%. However, the changes of LA-B (antero-posterior diameter), LV-D1 (basal dimension), RA-B (minor dimension), and RV-D2 (mid cavity dimension) were relatively more stable than other diameters during the cardiac cycle. The maximum LA-B diameter, LV-D1 diameter, RA-B diameter, and RV-D2 diameter as well as the maximum interventricular septum thickness were acquired. Heart rate (HR) and smoking were potential indicators of LV-D2 (mid cavity dimension), while HR and LV myocardial mass were potential indicators of LV-D3 (apical-basal dimension). In phase 45%, the cut-off value of LA-B was 37.12 mm, with high sensitivity for predicting LA enlargement. Choosing the adaptive cardiac phase for evaluating cardiac chamber dimensions and wall thickness obtained by cardiac CT could provide a more accurate clinical measurement of the heart.

Dosimetric feasibility study (“proof of concept”) of refractory ventricular tachycardia radioablation using proton minibeams

PurposePreclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. Material and methodsAn arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. ResultsThe average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. ConclusionThis proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

Diagnosis and treatment of arrhythmogenic cardiomyopathy in children

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable. Conclusions: ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

Abstract 2776: Exploring the differences between brain tumor initiating cell extracellular vesicles and secreted factors that influence the tumor microenvironment

Abstract Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults. Within the tumor, there is a subtype of cells deemed brain tumor initiating cells (BTICs), which contribute to tumor progression, therapy resistance, and tumoral heterogeneity. The tumor microenvironment, surrounding tumors, contains an ecosystem of cells in which BTICs can interact with and further promote tumor progression. In the lateral wall of the lateral ventricles, the neurogenic niche of the subventricular zone (SVZ), contains neural progenitor cells (NPCs) that self-renew and generate highly migratory neuroblasts. Interestingly, GBM tumors proximal to the SVZ are more proliferative, migratory, and negatively impact the survival of patients. We have previously observed that the presence of GBM induces reciprocal changes to the SVZ altering its neurogenic capacity and resulting in a more proliferative tumor. BTICs share similar self-renewal capacity to NPCs and may exert intercellular communication resulting in increased malignancy features. The mechanisms of intercellular communication, present in the SVZ include paracrine, autocrine, direct cell contact, gap junctions, nanotubes, and more recently extracellular vesicles (EVs). However, the exact mechanisms of how BTICs communicate with NPCs is not well understood. EVs are a heterogenous group of cell-derived membranous structures that serve as means of intercellular communication, allowing for cells to exchange proteins, lipids, RNA, and other genetic material. Cancer cells release higher amounts of EVs than non-malignant cells, and these EVs help communicate with other nearby cells, leading to promotion of tumorigenesis. We have observed that BTICs-derived EVs increase the proliferation of human NPCs, while altering their morphology and expression of stem cell markers. These effects are not observed when NPCs are treated with vesicle-free BTIC-derived secreted factors. To investigate the distinctions between BTIC secreted factors and protein cargo contained in BTIC-EVs, we employ the proximity protein labelling system, TurboID, and express this system in BTIC-EVs. The overarching goal of this project is to characterize BTIC-derived EV cargo to identify proteins that modify the GBM tumor microenvironment. We hypothesize that the phenotype of non-cancer NPCs is altered by distinct protein cargo contained in BTIC-derived EVs. The results of these experiments will help us to elucidate what BTIC-specific EV cargo impacts the tumor microenvironment, with the potential of revealing therapeutic targets for GBM. Citation Format: Marissa Russo, Maria Jose Ulloa Navas, Emily Norton-Ramos, Alfredo Quiñones Hinojosa, Hugo Guerrero Cazares. Exploring the differences between brain tumor initiating cell extracellular vesicles and secreted factors that influence the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2776.

Myocardial Infarction Seen Tardively Complicated by Ventricular Septal Rupture Extending to the Right Ventricule: A Dilemmatic Scenario

Ventricular septal rupture (VSR) is an uncommon but well-recognized mechanical complication of acute myocardial infarction (MI). Mortality without intervention is 70% in intrahospital at 30 days, and 90% at one year due to cardiogenic shock. Transthoracic echocardiography (TTE) is the choice tool in the diagnosis and evaluation of VSR. We report an original case of a 72-year-old patient diagnosed with myocardial infarction of the inferior wall of the left ventricle, complicated by the rupture of its basal segment aneurysm extending to the right ventricle. After which standard drug treatment was prescribed. Inferior wall myocardial infarction complicated with VSR at its basal segment is a rare mechanical complication of MI and this clinical case shows a rare location of VSR compared to forms described in the literatures. On the third day, the patient died from refractory cardiogenic shock, and neurological complications which could have been prevented by surgery. Treatment of VSR secondary to MI is an emergency based on either an open heart surgery or percutaneous intervention inorder to reduce morbi-mortality rate.