Left Ventricular Internal Diameter In Diastole Research Articles

Fuyu Decoction ameliorates myocardial fibrosis in rat model of heart failure by regulating Nrf2/GPX4-mediated ferroptosis

This study aims to investigate the effect and mechanism of Fuyu Decoction(FYD) in the treatment of myocardial fibrosis in the rat model of heart failure(HF). Sixty Wistar rats were randomized into a modeling group(n=50) and a sham group(n=10). A post-myocardial infarction HF model was established by ligating the left anterior descending coronary artery in rats. The successfully modeled rats were assigned into model, low-dose(2.5 g·kg~(-1)) FYD(FYD-L), high-dose(5.0 g·kg~(-1)) FYD(FYD-H), and FYD+Nrf2 inhibitor(ML385, 30 mg·kg~(-1)) groups(n=10). FYD was administrated by gavage and ML385 by intraperitoneal injection. The rats in the sham and model groups were administrated with equal amounts of normal saline by gavage. After 8 weeks of intervention, the cardiac function indicators were measured, and the myocardial tissue morphology and collagen deposition were observed. The positive expression of collagens Ⅰ and Ⅲ, apoptosis, and oxidative stress were examined, and the levels of Fe~(2+) and reactive oxygen species(ROS) were determined. The protein levels of nuclear factor erythroid 2-related factor 2(Nrf2), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), and acyl-coenzyme A synthase long chain family member 4(ACSL4) in the myocardial tissue were determined. Compared with sham group, the model group showed decreased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased left ventricular end internal dimension in systole(LVIDs), left ventricular internal diameter in diastole(LVIDd), and myocardial collagen deposition, positive expression of collagens Ⅰ and Ⅲ, elevated apoptosis rate and malondialdehyde(MDA), Fe~(2+), and ROS levels, lowered superoxide dismutase(SOD) and glutathione peroxidase(GSH) levels, down-regulated protein levels of Nrf2, SLC7A11, and GPX4, and up-regulated protein level of ACSL4. Compared with the model group, the above indicators were restored by FYD. Moreover, ML385 reversed the protective effect of FYD on myocardial fibrosis in HF rats. In conclusion, FYD can inhibit ferroptosis by activating the Nrf2/GPX4 pathway, thereby ameliorating myocardial fibrosis in HF rats.

Left ventricular strain and myocardial work in short-term peritoneal dialysis patients

Background Initiation of dialysis encompasses new cardiovascular challenges on patients with end-stage renal disease (ESRD). This study used two-dimensional speckle-tracking echocardiography (2D-STE) to investigate the change of left ventricular (LV) myocardial function undergoing peritoneal dialysis (PD) within 1–3 months. Methods A total of 56 patients with ESRD and 27 healthy controls were enrolled in this prospective study. Mean duration of PD was 44.41 ± 16.44 days. We evaluated LV myocardial function of patients with ESRD in baseline and within 1–3 months after PD by 2D-STE with global longitudinal strains (GLS) and myocardial work (MW). Based on the level of serum phosphate before PD, patients were divided into two groups: the group with normal serum phosphate or hyperphosphatemia. Results Compared with healthy controls, patients with ESRD had impaired GLS (p < .001) and increased global work index (GWI) (p = .034), global constructive work (GCW) (p < .001), global wasted work (GWW) (p < .001), and lower global work efficiency (GWE) (p = .002). After PD therapy, GWI (p = .001), GCW (p < .001), and GWW (p = .023) decreased and closed to healthy subjects (p > .05) and no significant improvement was observed in GLS (p = .387). GLS of basal segments worsened in the hyperphosphatemia group (p = .005) and GWW reduced remarkably in the group with normal serum phosphate after PD treatment (p = .008). The change of left ventricular internal diameter in diastole (LVIDd) was the only parameter influenced GWI in post-dialysis patients (β = 0.324, p = .013). Conclusions Short-term PD treatment improved LV MW in ESRD patients. They benefited more when receiving treatment before the increase of serum phosphorus.

Efficacy and mechanism of Xuefu Zhuyu Decoction on model rats of coronary heart disease with heart blood stasis syndrome based on metabolomics

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.

Echocardiographic reference intervals and cut-off values to diagnose dilated cardiomyopathy in guinea pigs (Cavia porcellus)

The objective of this study was to establish reference intervals in healthy guinea pigs and to calculate optimal cut-off values for several M-Mode parameters to diagnose dilated cardiomyopathy (DCM) phenotype. This prospective study included 146 guinea pigs. The apparently healthy group included 92 animals and was used to create reference intervals for left ventricular internal diameter in diastole (LVIDd), left ventricular internal diameter in systole (LVIDS), E-point-to-septal separation (EPSS), diastolic wall thickness and left atrium and aorta. Allometric scaling was used to normalize LVIDd(-n) and LVIDs(-n) to body weight with a scaling exponent (BWexp). The DCM phenotype group included 54 subjects and was used to calculate optimal cut-off values of several M-mode parameters. Guinea pigs with DCM phenotype had significantly larger measurements of LVIDd, LVIDs and EPSS, as well as lower FS and wall thicknesses compared to apparently healthy guinea pigs. Allometric scaling exponents to normalize LVIDd and LVIDs to BW (g) were 0.336 and 0.346, respectively. The highest area under the curve (AUC) to diagnose DCM were found for LVIDs-n (cut-off value >0.74 mm, AUC 0.996), FS (cut-off value <29%, AUC 0.995), LVIDd-n (cut-off value >1.07 mm, AUC 0.980) and EPSS (cut-off value >1.4 mm, AUC 0.944). M-mode and 2D reference intervals for guinea pigs are presented, including lower and upper limits. Diagnosis of DCM phenotype in guinea pigs can be established using parameters known to be useful in other species, namely LVIDs, LVIDs-n, FS, LVIDd, LVIDd-n and EPSS.

Echocardiographic evaluation of right heart pressure changes in healthy newborns and its follow-up till 12 weeks of life

Background: Right ventricular (RV) pressure undergoes a series of changes from foetal to neonatal period on both left and right heart. Pulmonary velocity acceleration time (PVAccT) measured by trans-thoracic echocardiography has been established as a reliable indicator of RV pressure measurement in neonates. This study aims to throw some light into the changes in the RV pressure by serial PVAccT measurements in the initial 12 weeks of life. Materials and Methods: A cross sectional study was carried out among term new-borns until 12 weeks of age and serial changes in the PVAccT values were recorded, reflecting the mean pulmonary artery pressure (MPAP), and the left ventricular internal diastolic diameter (LVIDD), left atrial diameter (LAD), right ventricular outflow tract (RVOT), right ventricular free wall thickness (RVFWT). Results: There was gradual increase in the mean value of PVAccT with age from birth i.e., 1-3 days (70.08±18.62ms) to 3 months (86.23±17.31ms) (p=&lt;0.05). Mean value of right ventricular outflow tract proximal diameter was also seen to have an increase from day 1-3 (0.92±0.19cm) to 3 months of age (1.09±0.01cm) (p= &lt;0.001). There was an overall decrease in the mean value of the RVFWT from day 1-3 (0.37±.07 cm) to 3 months (0.27±0.07cm) of age after an increase at 1 month (p=&lt;0.05). Statistically significant increase in mean LAD from 1.18±0.29cm to 1.40±0.35 cm and LVIDD from 1.54±0.31cm to1.96±0.27 was seen from birth to 3 months of age. Conclusion: Changes in PVAcct and RV pressure with time from birth to 3 months of age will aid in early diagnosis of persistent pulmonary artery hypertension of new-born (PPHN) or pulmonary arterial hypertension (PAH).

Plasma N-terminal pro-atrial natriuretic peptide concentrations are affected by dehydration in healthy dogs.

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations may be affected by the hydration status. This study aimed to evaluate the effect of dehydration on plasma NT-proANP and NT-proBNP concentrations in healthy dogs. This prospective study included five clinically healthy dogs. Furosemide was administered intravenously at 2-4 mg/kg every 1-2 hours until completion of the dehydration model. The dehydration model was considered complete when weight loss was ≥5% and findings of dehydration on physical examination were observed. Plasma NT-proANP and NT-proBNP concentrations were compared at three-time points: before the dehydration model was created (point 1), at the completion of the dehydration model (point 2), and when dehydration was judged to have improved (point 3). Association between plasma NT-proANP and NT-proBNP concentrations, and each clinical variable (physical examination, blood pressure, blood chemistry, blood gases, and echocardiography) was assessed using linear regression analysis. Plasma NT-proANP concentration decreased significantly from point 2 to point 1 (p < 0.05), whereas plasma NT-proBNP concentration showed a decreasing trend but did not differ significantly between points 1 and 2. Plasma NT-proANP concentration correlated significantly with body weight (R2 = 0.178) and plasma NT-proBNP concentration (R2 = 0.284) (p < 0.05, respectively), and plasma NT-proBNP concentration correlated significantly with electrolytes (sodium, R2 = 0.439; potassium, R2 = 0.444; and chloride, R2 = 0.419), and echocardiographic parameters [diastolic left ventricular internal diameter (LVIDd) R2 = 0.519; weight-standardized LVIDd, R2 = 0.535] (p < 0.01, respectively). The plasma NT-proANP concentrations decreased with dehydration. However, the plasma NT-proBNP concentration did not change with mild dehydration and reflected left ventricular morphology.

Influence of Dorper lamb development from birth to 120 days of age on clinical and echocardiographic parameters

The expansion of the sheep model in research represents an attractive and economically beneficial academic reason for investigations in sheep echocardiography. The present study aimed to evaluate the clinical and echocardiographic parameters in Dorper lambs during the developmental period. Emphasis was placed on the use of the species in translational research for the echocardiographic diagnosis of congenital heart diseases, which can contribute to improvements in interventionist techniques. Ten Dorper lambs were evaluated at the following time points: 24 h after birth and 7, 14, 21, 30, 60, 90 and 120 days of age. Clinical parameters were compiled, and echocardiogram records were obtained without sedation. Rectal temperature was lower on the first day compared to the others. From 21 days of life, there was a reduction in HR, with differences between time points. Mean and systolic blood pressure differed, with the highest values at 90 and 120 days of age. The thickness of the interventricular septum in diastole (IVSd) increased as age progressed, with the highest value at 120 days of age, and the same occurred for LVIDd (left ventricle internal diameter in diastole), LVFWd (left ventricular free wall thickness in diastole), IVSs (interventricular septum thickness in systole), LVIDs (left ventricle internal diameter in systole) and LVFWs (left ventricular free wall thickness in systole). There were differences in the size of the LA, Ao and LA/Ao ratio, which were greater at 90 days and 120 days of age. Echocardiographic changes accompany the development of lambs, where changes in echocardiographic parameters are evident with advancing age. The echocardiographic measurements in lambs obtained in the present study are similar to those in newborns.

Mechanism of Kaixin Powder prescriptions Buxin Decoction regulating PI3K/AKT signaling pathway to protect cardiovascular system: based on network pharmacology and experimental verification

This study established the EA.hy926 cell myocardial ischemia model to compare the effects of two Kaixin Powder prescriptions, Buxin Decoction(BXD) and Dingzhi Pills(DZP), at three dosages(500, 200, and 100 μg·mL~(-1)) on the cell viability. Further, the public databases(TCMSP, TCMID, SYMMAP, and STRING) and the network pharmacology methods such as KEGG pathway enrichment were employed to decipher the possible molecular mechanism of BXD in exerting the cardioprotective effect. The pharmacological effect of BXD was evaluated with the rat model of isoprenaline(ISO)-induced myocardial ischemia. The expression levels of proteins involved in the phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) signaling pathway were measured by Western blot. BXD significantly increased the viability of EA.hy926 cells, showing the performance superior to DZP. The network pharmacology analysis predicted that BXD might exert cardiac protection through the PI3 K/AKT signaling pathway. The in vivo experiment on rats showed that BXD treatment significantly increased the cardiac ejection fraction(EF), fractional shortening(FS), diastolic left ventricular anterior wall(LVAWd), systolic left ventricular anterior wall(LVAWs), and diastolic left ventricular posterior wall(LVPWd), significantly decreased the beat per minute(BPM) and diastolic left ventricular internal diameter(LVIDd), and significantly improved the ST segment in the electrocardiogram. The pathological results(Masson staining) showed that BXD restored the myocardial thickness, decreased the collagen fiber, increased the muscle fiber, and reduced the infarct area to alleviate myocardial ischemia. Furthermore, BXD lowered the serum levels of inflammatory cytokines [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)] and myocardial enzymes [creatine kinase(CK) and lactate dehydrogenase(LDH)], increased the p-AKT/AKT ratio, up-regulated the protein levels of PI3 K, NF-κB, IKK-α, and Bcl-xl, and down-regulated that of the apoptotic protein Bax. In conclusion, BXD may exert cardiac protection effect by regulating the PI3 K/AKT signaling pathway.

Utility of Follow-Up Echocardiograms in Uncomplicated PDA Device Closures Performed After Infancy.

IntroductionGuidelines recommend lifelong follow-up with transthoracic echocardiograms (TTE) for patients who had a patent ductus arteriosus (PDA) device closure via catheterization. The goal of this study was to determine the utility of follow-up TTE in patients who underwent an uncomplicated PDA device closure after infancy.MethodsChart review was performed on patients who had a PDA closure ≥ 1 year of age between 1/1/2002 and 6/1/2020. Patients were excluded if they had other congenital heart disease, did not have a follow-up TTE ≥ 6 months after procedure, had a residual PDA or velocity > 2.0 m/s in the left pulmonary artery (LPA) or descending aorta (DAo) on the first TTE ≥ 6 months after device placement. Time points included the initial TTE after the procedure, first TTE ≥ 6 months after procedure, and the most recent TTE.ResultsA total of 189 patients met the study criteria. The median age and weight at initial procedure were 2.7 (1.0–64.7) years and 12.5 (3.4–69.2) kg. Most recent TTE was performed 2.0 (0.4–17.0) years after PDA closure. There were no significant differences in fractional shortening (36.4 ± 5.0% vs. 36.9 ± 5.6%) or LPA velocity (1.1 ± 0.4 m/s vs. 1.1 ± 0.4 m/s) from initial to most recent TTE, respectively. Left ventricular internal diastolic diameter Z-score significantly decreased (1.4 ± 1.8 vs. − 0.01 ± 1.2, p < 0.01) and DAo peak velocity significantly increased (1.2 ± 0.3 m/s vs. 1.3 ± 0.3 m/s, p = 0.02) from initial to most recent TTE, respectively. No patient died or underwent an intervention on the LPA or DAo for stenosis. Seventy-five patients had a total of 208 repeat TTE > 1 year after PDA procedure with no change in clinical management.ConclusionsIn patients who underwent an uncomplicated PDA closure after infancy, TTE parameters improved or stayed within normal limits on the most recent TTE. Repeat lifetime TTEs after 1-year post-device placement in this population may not necessarily be needed if there are no clinical concerns.

Left Ventricular Assist Device as a Bridge to Recovery: Single Center Experience of Successful Device Explantation.

Continuous-flow left ventricular assist devices (CF-LVAD) have been shown to enhance reverse remodeling and myocardial recovery in certain patients allowing for device removal. We sought to analyze the characteristics and describe outcomes of patients who underwent CF-LVAD explantation at a large academic center. We retrospectively identified all patients who underwent CF-LVAD explants due to recovery from 2006 to 2019. Patient baseline characteristics and data on pre- and postexplant evaluation were collected and analyzed. Of 421 patients who underwent CF-LVAD implantation, 13 underwent explantation (3.1%). Twelve HeartMate II and one HeartWare LVAD were explanted. All patients had nonischemic cardiomyopathy. Median time from heart failure diagnosis to LVAD implant was 12 months (interquartile range [IQR], 2-44) and the median time supported on LVAD was 22 months (IQR, 11-28). Two patients died within 30 days of explant. Three additional patients died during the follow-up period and all were noted to be nonadherent to medical therapy. After a mean follow-up duration of 5 years, overall survival was 52%. Mean pre-explant ejection fraction was 49%, which decreased at most recent follow-up to 32%. Mean pre-explant left ventricular internal diameter in diastole (LVIDD) was 4.37 cm and increased to 5.52 cm at most recent follow-up. Continuous-flow left ventricular assist device explantation is feasible and safe in select patients.

Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning.

BackgroundCardiovascular disorders in general are responsible for 30% of deaths worldwide. Among them, hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that is present in about 1 of 500 young adults and can cause sudden cardiac death (SCD).ObjectiveAlthough the current state-of-the-art methods model the risk of SCD for patients, to the best of our knowledge, no methods are available for modeling the patient's clinical status up to 10 years ahead. In this paper, we propose a novel machine learning (ML)-based tool for predicting disease progression for patients diagnosed with HCM in terms of adverse remodeling of the heart during a 10-year period.MethodsThe method consisted of 6 predictive regression models that independently predict future values of 6 clinical characteristics: left atrial size, left atrial volume, left ventricular ejection fraction, New York Heart Association functional classification, left ventricular internal diastolic diameter, and left ventricular internal systolic diameter. We supplemented each prediction with the explanation that is generated using the Shapley additive explanation method.ResultsThe final experiments showed that predictive error is lower on 5 of the 6 constructed models in comparison to experts (on average, by 0.34) or a consortium of experts (on average, by 0.22). The experiments revealed that semisupervised learning and the artificial data from virtual patients help improve predictive accuracies. The best-performing random forest model improved R2 from 0.3 to 0.6.ConclusionsBy engaging medical experts to provide interpretation and validation of the results, we determined the models' favorable performance compared to the performance of experts for 5 of 6 targets.

Cardiac Involvement among HIV-positive Individuals less than 18 years of Age on Antiretroviral Therapy- An Observational Study from a Rural Tertiary Care Hospital, West Bengal, India

Introduction: With advancement of medical science, individuals diagnosed with Human Immunodeficiency Virus (HIV) infections are getting treated earlier and a fewer of them develop Acquired Immunodeficiency Syndrome (AIDS)-related complications. But the downside is that there is an earlier onset and higher relative risks for different chronic diseases including cardiovascular diseases. Aim: To determine the proportion and pattern of cardiac involvements among children undergoing treatment for HIV infection and to correlate various cardiac findings with duration of Antiretroviral Therapy (ART) among them. Materials and Methods: An observational cross-sectional study was conducted among 136 HIV infected patients attending Paediatrics and General Medicine Outpatient Departments of North Bengal Medical College and Hospital (NBMCH) from October 2019 to March 2021. All patients were assessed clinically and underwent two dimensional (2D) echocardiography, Motion mode (M mode) and colour doppler for assessing cardiac involvement. Collected data were analysed using Statistical Package for the Social Sciences (SPSS) software version 22.0 and Pearson’s Correlation test was applied to test association between duration of ART and different echocardiographic parameters. Results: The mean age of the study participants was 10.14 years and the mean duration of ART was 49.18 months. Almost half (48.5%) of the HIV-positive individuals had cardiovascular findings. The most common echocardiographic change noted in patients was diastolic dysfunction 39 (28.7%) followed by Pericardial Effusion (PE) 29 (21.3%) and systolic dysfunction 28 (20.6%). Statistically significant positive correlation between changes in the values of Left Ventricular Internal Diameter in Diastole (LVIDD) (r=0.982), Left Atrium (LA) (r=0.634), mean Pulmonary Artery Pressure (mPAP) (r=0.200) with duration of ART was noted. Negative correlation was seen between duration of ART with ejection fraction (r=-0.984) and Tricuspid Annular Plain Systolic Excursion (TAPSE) (r=-0.438). This indicated that all these important cardiological parameters became worser with advancement of treatment. Conclusion: Cardiac involvements among HIV positive individuals undergoing ART were still high. There was definite correlation between cardiac involvement and duration of ART.

Iron deficiency is an independent risk factor of increased myocardial energy expenditure in chronic heart failure patients

Chronic heart failure (CHF) is a major public health burden and is associated with high morbidity, mortality, and cost. Recent studies demonstrated iron metabolism and myocardial energy metabolism were altered in CHF patients. In this study, we aimed to analyze the effects and correlations of iron metabolism on myocardial energy metabolism in CHF. One hundred and thirty patients with CHF [age: 66.2±11.5 years, males: 58.5% and New York Heart Association (NYHA) class (II/III/IV): 67/43/20] were included. Serum concentrations of ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were quantified as the indexes of iron metabolism, and echocardiography was used to assess myocardial energy expenditure (MEE) levels. Iron deficiency (ID) was defined as ferritin <100 or 100-300 µg/L with Tsat <20%. Patients with CHF were divided into two groups based on iron status. The prevalence of ID in CHF was 36.9%, and increased with the severity of CHF, reaching 80.0% in those with NYHA class IV (NYHA class II/III/IV: 17.9% vs. 46.5% vs. 80.0%, P=0.000). The demographic characteristics [age, sex, body mass index (BMI), blood pressure, and heart rate] and hemoglobin (HGB) concentrations in two groups were similar (all P>0.05). MEE was significantly higher in the ID group (92.7±23.0 vs. 65.6±20.8 cal/min, P=0.000), while NYHA classes II and III was significantly higher in the ID group (71.6±16.4 vs. 60.3±14.8 cal/min, P=0.022; 88.9±10.4 vs. 69.1±20.1 cal/min, P=0.000). In univariable linear regression models, the presence of ID, higher NYHA class, increased N-terminal pro-B-type natriuretic peptide (NT-proBNP), sTfR, left ventricular internal diastolic diameter (LVIDd), as well as reduced ferritin, Tsat levels, and lower left ventricular ejection fraction (LVEF) were associated with elevated MEE levels (all P<0.05). In multivariable regression models, the presence of ID, reduced Tsat. and increased sTfR remained independent predictors of elevated MEE levels after adjustment for all variables that showed a significant association with MEE (all P<0.05). The prevalence of ID is high in CHF and is associated with the severity of cardiac dysfunction. The presence of ID as well as reduced Tsat and increased sTfR concentrations are associated with elevated MEE levels in CHF.

Tanshinone IIA Improves Ventricular Remodeling following Cardiac Infarction by Regulating miR-205-3p.

Objective To illustrate the role of tanshinone IIA (TSN) in regulating cardiac structure and function following myocardial infarction (MI) and the involvement of miR-205-3p in TSN-induced antifibrosis effect on ventricular remodeling. Patients and Methods. One hundred MI patients were randomly assigned into two groups, and they were treated with TSN (TSN group, n = 50) or conventional therapy (control group, n = 50). Plasma levels of miR-205-3p and TGF-β1 were detected in each patient. Echocardiography was conducted in each patient at post-MI 1 day, 2 weeks, and 4 weeks, respectively, for recording LVIDd (left ventricular internal-diastolic diameter), LVIDs (left ventricular internal-systolic diameter), and LVEF (left ventricular ejection fraction). The interaction between miR-205-3p and TGF-β1 was examined by the RNA-Binding Protein Immunoprecipitation (RIP) assay. After induction of TGF-β1 and/or 10 μL of TSN in cardiac fibroblasts, relative levels of miR-205-3p, Col1a1, and Col3a1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results Compared with the control group, miR-205-3p and TGF-β1 were downregulated in plasma of MI patients in the TSN group. In the TSN group, LVIDd and LVIDs were reduced, and EF was enhanced at 2 weeks and 4 weeks compared with that at post-MI 1 day. miR-205-3p could negatively interact with TGF-β1. TSN induction abolished the regulatory effects of TGF-β1 on downregulating miR-205-3p and upregulating Col1a1 and Col3a1 in cardiac fibroblasts. Conclusions Through upregulating miR-205-3p and downregulating TGF-β1, TSN alleviates cardiac fibrosis and improves ventricular remodeling following MI.

Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

Background Tingli Dazao Xiefei decoction (TDXD) has been shown to have a therapeutic effect on heart failure (HF). Nevertheless, its molecular mechanism for treating HF is still unclear. Materials and Methods TDXD and HF targets were collected from the databases, and protein-protein interaction (PPI) analysis and enrichment analysis were performed on the overlapping targets. Then, AutoDock was employed for molecular docking. Finally, we used the left anterior descending coronary artery (LAD) ligation to induce HF model rats for in vivo experiments and verified the effect and mechanism of TDXD on HF. Results Network pharmacological analysis showed that the main active components of TDXD in treating HF were quercetin, kaempferol, beta-carotene, isorhamnetin, and beta-sitosterol, and the core targets were IL-6, VEGFA, TNF, AKT1, and MAPK1. Multiple gene functions and signaling pathways were obtained by enrichment analysis, among which inflammation-related, PI3K/Akt, and MAPK signaling pathways were closely related to HF. Furthermore, the molecular docking results showed that the core targets had good binding ability with the main active components. Animal experiments showed that TDXD could effectively improve left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS), decrease left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs), reduce the area of myocardial fibrosis, and decrease serum BNP, LDH, CK-MB, IL-6, IL-1β, and TNF-α levels in HF rats. Meanwhile, TDXD could upregulate the expression of Bcl-2, downregulate the expression of Bax, and reduce cardiomyocyte apoptosis. At the same time, it was verified that TDXD could significantly decrease the expression of PI3K, P-Akt, and P-MAPK. Captopril showed similar effects. Conclusions Combining network pharmacological analysis and experimental validation, this study verified that TDXD could improve cardiac function and protect against cardiac injury by inhibiting the activation of PI3K/Akt and MAPK signaling pathways.

LVAD decommissioning for myocardial recovery: Long-term ventricular remodeling and adverse events

Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown. This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant. During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p=0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p=0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years. LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy.

Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents.

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.

Echocardiographic parameters in 50 healthy English bulldogs: preliminary reference intervals

Introduction/objectivesThe objective of the study was to provide echocardiographic reference intervals for English bulldogs (EBs) and to assess if age, sex, body weight (BW), and heart rate have an influence on echocardiographic variables. AnimalsWe prospectively enrolled client-owned EBs that were considered healthy based on unremarkable history, normal physical examination, six-lead electrocardiography, and transthoracic echocardiography. Materials and methodsBreed-related reference intervals were provided, and associations between age, sex, BW, and heart rate and echocardiographic variables were tested using a multivariate analysis. Allometric scales were generated for echocardiographic variables showing correlation with BW. Moreover, echocardiographic variables obtained in our population of EBs and previous published reference ranges were compared. ResultsEchocardiographic reference intervals were generated from 50 healthy adult EBs. As per the multivariate analysis, left atrial diameter (p = 0.015), left ventricular internal end diastolic diameter (p = 0.002), aortic valve annulus (p = 0.032), and pulmonary valve annulus (p = 0.017) resulted influenced by BW, and reference intervals were generated using allometric scales. Our study suggests that EBs tend to have a smaller aortic root and sphericity index than other breeds. In addition, EBs seem to have smaller indexed left ventricular volumes and higher left ventricular ejection fraction than boxers and Doberman. ConclusionPreliminary reference intervals in the EBs are reported, which might be helpful for accurate echocardiographic interpretation and screening purposes in this breed.

Cardiac Remodeling in Patients with Childhood-Onset Craniopharyngioma - Results of HIT-Endo and KRANIOPHARYNGEOM 2000/2007

Hypothalamic obesity caused by childhood-onset craniopharyngioma results in long-term cardiovascular morbidity. Knowledge about clinical markers and risk factors is rare. A cross-sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 craniopharyngioma patients recruited in HIT-Endo and KRANIOPHARYNGEOM 2000/2007. BMI correlated with the thickness of interventricular septum in diastole (IVSd) (r=0.604, p<0.001) and left ventricular posterior wall thickness in diastole (LVPWd) (r=0.460, p=0.011). In multivariate analyses on risk factors for cardiac remodeling, sex hormone replacement therapy, BMI and male gender were positively correlated with increased left ventricular internal diameter in diastole (LVIDd), R2=0.596, F=10.323, p<0.001. BMI and insulin resistance were selected as significant independent determinants of IVSd, produced R2=0.655, F=29.441, p<0.001. Due to wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥18 years), BMI correlated with IVSd (r=0.707, p=0.003), LVPWd (r=0.592, p=0.020) and LVIDd (r=0.571, p=0.026). In the pediatric subgroup (age at study <18 years), no correlation between cardiac parameters and BMI was observed. Only LVIDd correlated with disease duration (r=0.645, p<0.001). All cardiac functions were within the normal range, indicating no association with functional impairments. We conclude that cardiac remodeling in patients with childhood-onset craniopharyngioma correlated with the degree of hypothalamic obesity, disease duration, sex hormone replacement therapy, male gender and insulin resistance. As echocardiography has limited sensitivity in patients with obesity, further research on more sensitive techniques for cardiac diagnostics in craniopharyngioma patients is warranted.

Androgen and Estrogen Receptor Activation Impacts Cardiac Function in a PCOS-Prone Rodent Model

Abstract Introduction: The global risk and incidence of cardiovascular disease (CVD) is increased in polycystic ovary syndrome (PCOS). Early risk factors and subclinical CVD includes atherogenic dyslipidemia, obesity, insulin resistance, blood pressure, atherosclerosis and impaired cardiac function. Androgen exposure is associated with onset of adiposity, impaired insulin-glucose and lipid metabolism, and cardiac dysfunction. The mechanisms of increased risk of CVD and cardiac dysfunction in PCOS related to hyperandrogenemia, AR and estrogen receptor (ER) activation remain unclear. Aim: The aim of this study was to investigate the effect of androgen treatment on cardiac AR and ER activation, fatty acid metabolism and cardiac function in a PCOS-prone rodent model. Methods: A PCOS-prone rodent model at 6 wks of age with obesity, apoB-remnant lipemia and insulin resistance, and controls were treated with testosterone for 12 weeks. Cardiac function was assessed using transthoracic doppler echocardiography (M-Mode 2D-imaging), lipogenic, AR, ER and other metabolic gene and protein expression were assessed using RTPCR and SDS-PAGE western blot. Results: PCOS-prone animals exhibited left ventricular (LV) hypertrophy, with increased LV mass to body weight (551.6 ± 38.85 mg vs 999 ± 96.17 mg, p&amp;lt;0.05), LV posterior wall diastolic diameter and LV internal diastolic diameter compared to controls. Isovolumetric relaxation time (IVRT) was prolonged (15.91 ± 1.591 msec vs 23.75 ± 0.722 msec, p&amp;lt;0.05). Mild systolic dysfunction was evidenced by increased isovolumetric contraction time (IVCT; 22.5 ± 1.348 msec vs 28.96 ± 1.248 msec, p&amp;lt;0.05) and decreased % ejection fraction and % fractional shortening in PCOS-prone compared to controls. T treatment increased LV mass, IVCT and IVRT in controls but did not exacerbate cardiac function in PCOS-prone animals. T treatment increased cardiac protein expression of PPAR-⍺ in PCOS-prone and controls, and T increased ACC in controls. AR protein expression tended to be reduced, and ER-⍺ was reduced in both T treated control and PCOS-prone animals. Conclusions: The PCOS-prone rodent model demonstrates early cardiac LV hypertrophy and diastolic-systolic dysfunction and T treatment alters fatty acid metabolism, and AR and ER activation are associated with altered cardiac morphology and function in the PCOS-prone and control conditions.