The study was conducted to investigate the mechanism of Xinyang Tablets( XYP) in modulating the fat mass and obesity-associated protein(FTO)/N6-methyladenosine(m6A) signaling pathway to ameliorate ventricular remodeling in heart failure(HF). A mouse model of HF was established by transverse aortic constriction(TAC). Mice were randomized into sham, model, XYP(low, medium, and high doses), and positive control( perindopril) groups(n= 10). From day 3 post-surgery, mice were administrated with corresponding drugs by gavage for 6 consecutive weeks. Following the treatment, echocardiography was employed to evaluate the cardiac function, and RT-qPCR was employed to determine the relative m RNA levels of key markers, including atrial natriuretic peptide( ANP), B-type natriuretic peptide( BNP), β-myosin heavy chain(β-MHC), collagen type I alpha chain(Col1α), collagen type Ⅲ alpha chain(Col3α), alpha smooth muscle actin(α-SMA), and FTO. The cardiac tissue was stained with Masson's trichrome and wheat germ agglutinin(WGA) to reveal the pathological changes. Immunohistochemistry was employed to detect the expression levels of Col1α, Col3α, α-SMA, and FTO in the myocardial tissue. The m6A modification level in the myocardial tissue was measured by the m6A assay kit. An H9c2 cell model of cardiomyocyte injury was induced by angiotensin Ⅱ(AngⅡ), and small interfering RNA(siRNA) was employed to knock down FTO expression. RT-qPCR was conducted to assess the relative m RNA levels of FTO and other genes associated with cardiac remodeling. The m6A modification level was measured by the m6A assay kit, and Western blot was employed to determine the phosphorylated phosphatidylinositol 3-kinase(p-PI3K)/phosphatidylinositol 3-kinase(PI3K) and phosphorylated serine/threonine kinase(p-Akt)/serine/threonine kinase(Akt) ratios in cardiomyocytes. The results of animal experiments showed that the XYP treatment significantly improved the cardiac function, reduced fibrosis, up-regulated the m RNA and protein levels of FTO, and lowered the m6A modification level compared with the model group. The results of cell experiments showed that the XYP-containing serum markedly up-regulated the m RNA level of FTO while decreasing the m6A modification level and the p-PI3K/PI3K and p-Akt/Akt ratios in cardiomyocytes. Furthermore, FTO knockdown reversed the protective effects of XYP-containing serum on Ang Ⅱ-induced cardiomyocyte hypertrophy. In conclusion, XYP may ameliorate ventricular remodeling by regulating the FTO/m6A axis, thereby inhibiting the activation of the PI3K/Akt signaling pathway.
Animals ; Ventricular Remodeling/drug effects* ; Heart Failure/physiopathology* ; Signal Transduction/drug effects* ; Mice ; Male ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Adenosine/analogs & derivatives* ; Myocytes, Cardiac/metabolism* ; Disease Models, Animal

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

OBJECTIVES: To compare perioperative and mid-term results of multiple versus single arterial off-pump coronary artery bypass grafting (OPCABG) in patients with impaired left ventricular function. METHODS: This study was conducted among 86 patients with a left ventricular ejection fraction (LVEF) <50%, who underwent OPCABG at our hospital between January, 2018 and December, 2021. Of these patients, 22 underwent OPCABG with multiple arterial grafts (multiple graft group) and 64 received a single arterial graft in OPCABG (single graft group). The preoperative, intraoperative, and perioperative data were collected, and the patients were followed up for a mean of 29.28±14.84 months. The perioperative outcomes and follow-up results of the patients were compared, and the factors influencing major adverse cardiovascular events (MACE) were identified using logistic regression. Kaplan-Meier analysis was used to compare the postoperative survival rate without MACE. RESULTS: The patients in multiple graft group had a significantly younger age than those in single graft group (P<0.05), but the other baseline data were similar between the two groups (P>0.05). Perioperative mortality, 24-h postoperative drainage volume, length of ICU stay, intubation time, and the incidence of new-onset atrial fibrillation were all similar between the two groups (P>0.05), but the rate of postoperative hypotension was significantly higher in multiple graft group (34.78% vs 11.54%, P=0.009). No significant differences were found in the incidence of MACE or echocardiographic data during the follow-up. Logistic regression identified the female sex (OR: 0.191, 95% CI: 0.049-0.075) and creatinine level (OR: 1.016, 95% CI: 1.000-1.033) as factors affecting postoperative MACE occurrence. Kaplan-Meier analysis showed no significant difference in MACE-free survival rate between the two groups. CONCLUSIONS OPCABG with multiple arterial grafts does not increase severe perioperative complications or the risk of mid-term MACE in patients with impaired left ventricular function.
Humans ; Follow-Up Studies ; Postoperative Complications/epidemiology* ; Ventricular Dysfunction, Left/physiopathology* ; Coronary Artery Bypass, Off-Pump/adverse effects* ; Male ; Female ; Ventricular Function, Left ; Middle Aged ; Risk Factors ; Aged ; Perioperative Period ; Stroke Volume

OBJECTIVES: To develop a risk prediction model for left ventricular adverse remodeling (LVAR) based on cardiac magnetic resonance (CMR) parameters in patients undergoing percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 329 acute STEMI patients undergoing primary PCI at 8 medical centers from January, 2018 to December, 2021 were prospectively enrolled. The parameters of CMR, performed at 7±2 days and 6 months post-PCI, were analyzed using CVI42 software. LVAR was defined as an increase >20% in left ventricular end-diastolic volume or >15% in left ventricular end-systolic volume at 6 months compared to baseline. The patients were randomized into training (n=230) and validation (n=99) sets in a 7∶3 ratio. In the training set, potential predictors were selected using LASSO regression, followed by univariate and multivariate logistic regression to construct a nomogram. Model performance was evaluated using receiver-operating characteristic (ROC) curves, area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: LVAR occurred in 100 patients (30.40%), who had a higher incidence of major adverse cardiovascular events than those without LVAR (58.00% vs 16.16%, P<0.001). Left ventricular global longitudinal strain (LVGLS; OR=0.76, 95% CI: 0.61-0.95, P=0.015) and left atrial active strain (LAAS; OR=0.78, 95% CI: 0.67-0.92, P=0.003) were protective factors for LVAR, while infarct size (IS; OR=1.05, 95% CI: 1.01-1.10, P=0.017) and microvascular obstruction (MVO; OR=1.26, 95% CI: 1.01-1.59, P=0.048) were risk factors for LVAR. The nomogram had an AUC of 0.90 (95% CI: 0.86-0.94) in the training set and an AUC of 0.88 (95% CI: 0.81-0.94) in the validation set. CONCLUSIONS LVGLS, LAAS, IS, and MVO are independent predictors of LVAR in STEMI patients following PCI. The constructed nomogram has a strong predictive ability to provide assistance for management and early intervention of LVAR.
Humans ; Percutaneous Coronary Intervention ; Prospective Studies ; ST Elevation Myocardial Infarction/diagnostic imaging* ; Ventricular Remodeling ; Magnetic Resonance Imaging ; Male ; Female ; Middle Aged ; Risk Factors ; Aged ; Risk Assessment

This article reviews the role of different types of T lymphocyte subpopulations in pathological cardiac fibrosis remodeling. T helper 17 (Th17) cells are implicated in promoting the development of pathological cardiac fibrosis remodeling, while regulatory T (Treg) cells exert an immunosuppressive functions as negative regulators, attributing to their interleukin-10 (IL-10) secretion and functional phenotype. Th1 and Th2 cells are involved in different stages of the inflammatory response in pathological cardiac fibrosis remodeling, and their influence varies according to the pathological mechanisms of different cardiac diseases. In addition, CD8⁺ T cells regulate the activation and polarization of macrophages, promote the secretion of granzyme B, induce cardiomyocyte apoptosis, and aggravate cardiac fibrosis post-myocardial infarction. Considering the limitation of cytokine modulation in clinical therapy of heart failure, targeting T-cell co-stimulatory molecules emerges as a promising strategy for treating pathologic cardiac remodeling. Future research will explore chimeric antigen receptor modified T cells (CAR-T cells) technology and targeted regulation of Treg cells quantity and phenotype, for both of which have the potential to become effective methods for treating heart disease.
Humans ; Fibrosis ; T-Lymphocytes, Regulatory/immunology* ; Ventricular Remodeling/immunology* ; Myocardium/immunology* ; Animals ; Th17 Cells/immunology* ; Interleukin-10/metabolism* ; Th1 Cells/immunology* ; Th2 Cells/immunology*

Objectives To learn the echocardiography skills of intensivists after receiving a basic critical care echocardiography training course, and investigate factors that may influence their performance. Methods We completed a web-based questionnaire that assessed the skills in ultrasound scanning techniques of intensivists who took a training course on basic critical care echocardiography held in 2019 and 2020. Mann-Whitney test was used to analyze the factors which might affect their performance on image acquisition, recognizing clinical syndrome, and measuring the diameter of inferior vena cava, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral.Results We enrolled 554 physicians from 412 intensive care units across China. Among them, 185 (33.4%) reported that they had 10%-30% chance of being misled by critical care echocardiography when making therapeutic decision, and 34 (6.1%) reported that the chance was greater than 30%. Intensivists who performed echocardiography under the guidance of a mentor and finished ultrasound scanning more than 10 times per week reported significant higher scores in image acquisition, clinical syndrome recognition, and quantitative measurement of inferior vena cava diameter, left ventricular ejection fraction and left ventricular outflow tract velocity-time integral than those without mentor and performing echocardiography 10 times or less per week respectively (all P < 0.05).Conclusion The skills in diagnostic medical echocardiography of Chinese intensivists after a basic echocardiographic training course remain low, and further quality assurance training program is clearly warranted.
Humans ; Clinical Competence ; East Asian People ; Echocardiography/standards* ; Stroke Volume ; Ventricular Function, Left ; Self-Assessment ; Physicians/standards* ; Internal Medicine/standards*

OBJECTIVES: To study the genetic characteristics, clinical characteristics, and prognosis of children with primary dilated cardiomyopathy (DCM). METHODS: A retrospective analysis was performed on the medical data of 44 children who were diagnosed with DCM in Hebei Children's Hospital from July 2018 to February 2023. According to the genetic testing results, they were divided into two groups: gene mutation-positive group (n=17) and gene mutation-negative group (n=27). The two groups were compared in terms of clinical data at initial diagnosis and follow-up data. RESULTS: Among the 44 children with DCM, there were 21 boys (48%) and 23 girls (52%). Respiratory symptoms including cough and shortness of breath were the most common symptom at initial diagnosis (34%, 15/44). The detection rate of gene mutations was 39% (17/44). There were no significant differences between the two groups in clinical characteristics, proportion of children with cardiac function grade Ⅲ or Ⅳ, brain natriuretic peptide levels, left ventricular ejection fraction, and left ventricular fractional shortening at initial diagnosis (P>0.05). The median follow-up time was 23 months, and 9 children (20%) died, including 8 children from the gene mutation-positive group, among whom 3 had TTN gene mutation, 2 had LMNA gene mutation, 2 had TAZ gene mutation, and 1 had ATAD3A gene mutation. The gene mutation-positive group had a significantly higher mortality rate than the gene mutation-negative group (P<0.05). CONCLUSIONS There is no correlation between the severity of DCM at initial diagnosis and gene mutations in children. However, children with gene mutations may have a poorer prognosis.
Male ; Female ; Humans ; Child ; Stroke Volume ; Retrospective Studies ; Ventricular Function, Left ; Phenotype ; Cardiomyopathy, Dilated/diagnosis* ; Mutation ; ATPases Associated with Diverse Cellular Activities/genetics* ; Membrane Proteins/genetics* ; Mitochondrial Proteins/genetics*

OBJECTIVE: To quantitatively assess cardiac functions in patients with cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance-feature tracking (CMR-FT) technique and evaluate the prognostic value of CMR-FT in patients with CA. METHODS: We retrospectively collected the data from 31 CA patients with systemic amyloidosis confirmed by Congo red staining and serum immunohistochemistry after extracardiac tissue biopsy undergoing CMR at our hospital from March, 2013 to June, 2021.Thirty-one age and gender matched patients with asymmetric left ventricular wall hypertrophy and 31 healthy individuals without organic or functional heart disease served as the controls.Radial, circumferential and longitudinal strains and strain rates of the left ventricle at the global level and in each myocardial segment (basal, middle and apical) were obtained with CMR-FT technique and compared among the 3 groups.The predictive value of myocardial strains and strain rates for all-cause mortality in CA patients was analyzed using a stepwise COX regression model. RESULTS: The left ventricular volume, myocardial mass, ejection fraction and cardiac output differed significantly among the groups (P < 0.05).Except for apical longitudinal strain, the global and segmental strains were all significantly lower in CA group than in HCM group (P < 0.05).The global and segmental strains were all significantly lower in CA group than in the healthy individuals (P < 0.05).The basal strain rates in the 3 directions were significantly lower in CA group than in the healthy individuals (P < 0.05), but the difference in apical strain rates was not statistically significant between the two groups.Multivariate stepwise COX analysis showed that troponin T (HR=1.05, 95%CI: 1.01-1.10, P=0.017) and middle peak diastolic circumferential strain rate (HR=6.87, 95%CI: 1.52-31.06, P=0.012) were strong predictors of death in CA patients. CONCLUSION Strain and strain rate parameters derived from CMR-FT based on cine sequences are new noninvasive imaging markers for assessing cardiac impairment in CA and cardiac function changes in HCM, and provide independent predictive information for all-cause mortality in CA patients.
Humans ; Retrospective Studies ; Magnetic Resonance Imaging, Cine/methods* ; Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Ventricular Function, Left ; Stroke Volume ; Amyloidosis/diagnostic imaging* ; Magnetic Resonance Spectroscopy ; Prognosis ; Predictive Value of Tests

OBJECTIVE: To investigate the effect of inhibitor of growth protein-2 (Ing2) silencing on angiotensin Ⅱ (AngⅡ)-induced cardiac remodeling in mice and explore the underlying mechanism. METHODS: An adenoviral vector carrying Ing2 shRNA or empty adenoviral vector was injected into the tail vein of mice, followed 48 h later by infusion of 1000 ng · kg^-1 · min^-1 Ang Ⅱ or saline using a mini-osmotic pump for 42 consecutive days. Transthoracic echocardiography was used to assess cardiac geometry and function and the level of cardiac hypertrophy in the mice. Masson and WGA staining were used to detect myocardial fibrosis and cross-sectional area of cardiomyocytes, and myocardial cell apoptosis was detected with TUNEL assay. Western blotting was performed to detect myocardial expressions of cleaved caspase 3, ING2, collagen Ⅰ, Ac-p53(Lys382) and p-p53 (Ser15); Ing2 mRNA expression was detected using real-time PCR. Mitochondrial biogenesis, as measured by mitochondrial ROS content, ATP content, citrate synthase activity and calcium storage, was determined using commercial assay kits. RESULTS: The expression levels of Ing2 mRNA and protein were significantly higher in the mice with chronic Ang Ⅱ infusion than in saline-infused mice. Chronic infusion of AngⅡ significantly increased the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) and reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the mice. Ing2 silencing obviously alleviated AngⅡ-induced cardiac function decline, as shown by decreased LVEDD and LVESD and increased LVEF and LVFS, improved myocardial mitochondrial damage and myocardial hypertrophy and fibrosis, and inhibited cardiomyocyte apoptosis. Chronic AngⅡ infusion significantly increased myocardial expression levels of Ac-p53(Lys382) and p-p53(Ser15) in the mice, and Ing2 silencing prior to AngⅡ infusion lessened AngⅡ- induced increase of Ac-p53(Lys382) without affecting p53 (ser15) expression. CONCLUSION Ing2 silencing can inhibit AngⅡ-induced cardiac remodeling and dysfunction in mice by reducing p53 acetylation.
Animals ; Mice ; Angiotensin II ; Tumor Suppressor Protein p53 ; Acetylation ; Stroke Volume ; Ventricular Remodeling ; Ventricular Function, Left ; Myocytes, Cardiac

INTRODUCTION: Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use. METHODS: A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE. RESULTS: We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046). CONCLUSION Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.
Humans ; Male ; Aged ; Female ; Coronary Artery Disease ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Myocardial Perfusion Imaging/methods* ; Calcium ; Stroke Volume ; Brain Ischemia ; Risk Factors ; Ventricular Function, Left ; Stroke ; Prognosis