Deletion of stimulator of interferons genes aggravated cardiac dysfunction in physiological aged mice.

BACKGROUND: Stimulator of interferons genes (STING) is crucial for innate immune response. It has been demonstrated that cGAS-STING pathway was the driver of aging-related inflammation. However, whether STING is involved in cardiac dysfunction during the physiological aging process remains unclear. METHODS: Gene expression profiles were obtained from the Gene Expression Omnibus database, followed by weighted gene co-expression network analysis, gene ontology analysis and protein network interaction analysis to identify key pathway and genes associated with aging. The effects of STING on cardiac function, glucose homeostasis, inflammation, and autophagy in physiological aging were investigated with STING knockout mice. RESULTS: Bioinformatics analysis revealed STING emerged as a hub gene of interest. Subsequent experiments demonstrated the activation of STING pathway in the heart of aged mice. Knockout of STING alleviated the inflammation in aged mice. However, Knockout of STING impaired glucose tolerance, inhibited autophagy, enhanced oxidative stress and aggravated cardiac dysfunction in aged mice. CONCLUSION: Although reducing inflammation, long-term STING inhibition by genetic ablation exacerbated cardiac dysfunction in aged mice. Given the multifaceted nature of aging and the diverse cellular functions of STING beyond immune regulation, the negative effects of targeting STING as a strategy to mitigate aging phenotype should be fully considered.

Inhibition of 5-alpha reductase attenuates cardiac oxidative damage in obese and aging male rats via the enhancement of antioxidants and the p53 protein suppression.

In aging and metabolic syndrome oxidative stress is a causative factor in the cardiovascular pathology. Upregulation of 5-⍺ reductase is associated with cardiac hypertrophy but how inhibition of 5-⍺ reductase affects cardiometabolic function during oxidative damage under those conditions is unclear. Our hypothesis was that Finasteride (Fin), a 5-⍺ reductase inhibitor, promotes an antioxidant response, leading to an improvement in cardiac function in obese and aging rats. Male rats were divided into 3 groups including normal diet (ND) fed rats, ND-fed rats treated with d-galactose (D-gal) to induce aging, and high-fat diet (HFD) fed rats to induce obesity. Rats received their assigned diet or D-gal for 18 weeks. At week 13, rats in each group were divided into 2 subgroups and received either a vehicle or Fin (5 mg/kg/day, oral gavage). Cardiometabolic and molecular parameters were subsequently investigated. Both D-gal and HFD successfully induced cardiometabolic dysfunction, oxidative stress, mitochondrial dysfunction, and DNA fragmentation. Fin treatment did not affect metabolic disturbances; however, it reduced cardiac sympathovagal imbalance, cardiac dysfunction through the inhibition of oxidative stress and promoted antioxidants, resulting in reduced p53 protein levels and DNA fragmentation. Surprisingly, Fin induced insulin resistance in ND-fed rats. Fin effectively improved cardiac function in both models by enhancing antioxidant levels, suppressing oxidative stress and DNA fragmentation. However, Fin treatment did not confer any beneficial effects on metabolic status. Fin administration effectively improved cardiac sympathovagal balance and cardiac function in rats with oxidative damage induced by either D-gal or HFD.

The impact of high-altitude migration on cardiac structure and function: a 1-year prospective study.

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

Using Doppler ultrasound to assess fetal cardiac function and pregnancy outcomes in obstetric antiphospholipid syndrome pregnancies: a case-control study.

PURPOSE: This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes. METHODS: In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy. CONCLUSION: MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making.

Maternal Ketone Supplementation Throughout Gestation Improves Neonatal Cardiac Dysfunction Caused by Perinatal Iron Deficiency.

Iron deficiency (ID) is common during gestation and in early infancy and has been shown to adversely affect cardiac development and function, which could lead to lasting cardiovascular consequences. Ketone supplementation has been shown to confer cardioprotective effects in numerous disease models. Here we tested the hypothesis that maternal ketone supplementation during gestation would mitigate cardiac dysfunction in ID neonates. Female Sprague Dawley rats were fed an iron-restricted or iron-replete diet before and throughout pregnancy. Throughout gestation, iron-restricted dams were given either a daily subcutaneous injection of ketone solution (containing ß-hydroxybutyrate [ßOHB]) or saline (vehicle). Neonatal offspring cardiac function was assessed by echocardiography at postnatal days (PD)3 and 13. Hearts and livers were collected post-mortem for assessments of mitochondrial function and gene expression profiles of markers oxidative stress and inflammation. Maternal iron restriction caused neonatal anemia and asymmetric growth restriction at all time points assessed, and maternal ßOHB treatment had no effect on these outcomes. Echocardiography revealed reduced ejection fraction despite enlarged hearts (relative to body weight) in ID offspring, resulting in impaired oxygen delivery, which was attenuated by maternal ßOHB supplementation. Further, maternal ketone supplementation affected biochemical markers of mitochondrial function, oxidative stress and inflammation in hearts of neonates, implicating these pathways in the protective effects conferred by ßOHB. In summary, ßOHB supplementation confers protection against cardiac dysfunction in ID neonates, and could have implications for the treatment of anemic babies.

Cardiovascular Adaptation in Fetal Growth Restriction: A Longitudinal Study From Fetuses at Term to the First Year of Life.

OBJECTIVE: To investigate longitudinal trends in fetal and offspring cardiovascular adaptation in fetal growth restriction (FGR). DESIGN: Prospective longitudinal study. SETTING: Fetal Medicine Unit. SAMPLE: Thirty-five FGR pregnancies and 37 healthy controls assessed as term fetuses (mean age 37 ± 1 weeks) and again in infancy (mean age 8 ± 2 months). METHODS: Conventional echocardiographic techniques, tissue Doppler imaging and speckle tracking echocardiography. MAIN OUTCOME MEASURES: Left ventricular (LV) and right ventricular (RV) geometry and function. Echocardiographic parameters were normalised by ventricular size adjusting for differences in body weight between groups. RESULTS: Compared to healthy controls, late FGR fetuses showed significant alterations in cardiac geometry with more globular LV chamber (LV sphericity index, 0.56 vs. 0.52), increase in biventricular global longitudinal systolic contractility (MAPSE, 0.29 vs. 0.25 mm; TAPSE, 0.42 vs. 0.37 mm) and elevated cardiac output (combined CO: 592 vs. 497 mL/min/kg, p < 0.01 for all). Indices of LV diastolic function in FGR fetuses were significantly impaired with myocardial diastolic velocities (LV A', 0.30 vs. 0.26 cm/s; IVS E', 0.19 vs. 0.16 cm/s) and LV torsion (1.2 vs. 3.5 deg./cm, p < 0.01 for all). At postnatal assessment, FGR offspring revealed persistently increased SAPSE (0.27 vs. 0.24 mm), LV longitudinal strain (-19.0 vs. -16.0%), reduced LV torsion (1.6 vs. 2.1 deg./cm) and elevated CO (791 vs. 574 mL/min/kg, p < 0.01 for all). CONCLUSIONS: Perinatal cardiac remodelling and myocardial dysfunction in late FGR fetuses is most likely due to chronic placental hypoxaemia. Persistent changes in cardiac geometry and function in FGR offspring may reflect fetal cardiovascular maladaptation that could predispose to long-term cardiovascular complications in later life.

Efficacy of Sacubitril Valsartan sodium tablets in patients with heart failure combined with pulmonary infection and long-term recurrence rate.

OBJECTIVE: To observe the therapeutic effect of Sacubitril Valsartan sodium tablets (SVST) on heart failure (HF) complicated by pulmonary infection (PI), and to provide a reference for future medication. METHODS: A total of 89 patients with HF complicated by PI who were treated at Dongying People's Hospital from January 2019 to May 2020 were selected as study subjects in this retrospective study. The control group consisted of 41 patients who received conventional treatment, while the study group included 48 patients who received SVST in addition to conventional treatment. The time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales in both groups were recorded. The levels of brain natriuretic peptide (BNP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and procalcitonin (PCT) were measured before and after treatment. Changes in cardiac function were observed, and the Clinical Pulmonary Infection Score (CPIS) and Sequential Organ Failure Assessment (SOFA) were used to assess PI. The clinical efficacy and adverse reactions were evaluated after treatment. Follow-up lasted 2 years, during which the readmission rate due to HF and mortality rate were calculated. RESULTS: Patients in the study group experienced a shorter time to disappearance/improvement of chest tightness, shortness of breath, cough, and moist rales compared to the control group (all P<0.05). The study group also showed reduced levels of BNP, IL-6, TNF-α, and PCT, as well as lower CPIS and SOFA scores after treatment (all P<0.05), with significantly improved cardiac function (P<0.05). Additionally, the total effective rate was higher in the study group than in the control group (P<0.05), and there was no significant difference in adverse reactions between the two groups (P>0.05). Follow-up revealed no difference in mortality between the two groups (P>0.05), but the study group had a lower readmission rate (P<0.05). CONCLUSION: SVST is effective in treating HF complicated by PI, ensures a good prognosis for patients, and is recommended for clinical use.

Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA.

Background: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism. Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI. Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-ß (TGF-ß) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-ß1in MI rats. Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-ß pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair.

Treatment with a combination of myricitrin and exercise alleviates myocardial infarction in rats via suppressing Nrf2/HO-1 antioxidant pathway.

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

Akkermansia Muciniphila supplementation improves hyperlipidemia, cardiac function, and gut microbiota in high fat fed apolipoprotein E-deficient mice.

Hyperlipidemia, obesity and gut dysbiosis are pivotal risk factors for atherosclerotic cardiovascular disease (ACVD). Supplementation of Akkermansia muciniphila (AKK) has also been proven to be effective in the prevention and treatment of obesity and other metabolic disorders. Here we found that AKK was more abundant in healthy control than ACVD patients via metagenomic sequencing on fecal samples. Subsequently, we investigated the role and underlying mechanism of AKK on obesity-associated atherosclerosis. AKK intervention partially reversed the exacerbation of atherosclerotic lesion formation in ApoE-/- mice by improving dyslipidemia. Interestingly, replenishment with AKK significantly enhanced cardiac function and reduced the body weight. It also reduced pro-inflammatory cytokine IL-6 and increased anti-inflammatory IL-10 in the circulation. Additionally, AKK colonization dramatically regulated gut microbiota and increased the abundance of Lactobacillaceae. Our findings have provided novel insights into the therapeutic potential of AKK as a beneficial microbe for treating atherosclerotic-associated cardiovascular diseases.

Imatinib­ and ponatinib­mediated cardiotoxicity in zebrafish embryos and H9c2 cardiomyoblasts.

Tyrosine kinase inhibitors (TKIs) offer targeted therapy for cancers but can cause severe cardiotoxicities. Determining their dose­dependent impact on cardiac function is required to optimize therapy and minimize adverse effects. The dose­dependent cardiotoxic effects of two TKIs, imatinib and ponatinib, were assessed in vitro using H9c2 cardiomyoblasts and in vivo using zebrafish embryos. In vitro, H9c2 cardiomyocyte viability, apoptosis, size, and surface area were evaluated to assess the impact on cellular health. In vivo, zebrafish embryos were analyzed for heart rate, blood flow velocity, and morphological malformations to determine functional and structural changes. Additionally, reverse transcription­quantitative PCR (RT­qPCR) was employed to measure the gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), established markers of cardiac injury. This comprehensive approach, utilizing both in vitro and in vivo models alongside functional and molecular analyses, provides a robust assessment of the potential cardiotoxic effects. TKI exposure decreased viability and surface area in H9c2 cells in a dose­dependent manner. Similarly, zebrafish embryos exposed to TKIs exhibited dose­dependent heart malformation. Both TKIs upregulated ANP and BNP expression, indicating heart injury. The present study demonstrated dose­dependent cardiotoxic effects of imatinib and ponatinib in H9c2 cells and zebrafish models. These findings emphasize the importance of tailoring TKI dosage to minimize cardiac risks while maintaining therapeutic efficacy. Future research should explore the underlying mechanisms and potential mitigation strategies of TKI­induced cardiotoxicities.

The Role and Underlying Mechanisms of Exercise in Heart Failure.

Heart failure is a prevalent and life-threatening syndrome characterized by structural and/or functional abnormalities of the heart. As a global burden with high rates of morbidity and mortality, there is growing recognition of the beneficial effects of exercise on physical fitness and cardiovascular health. A substantial body of evidence supports the notion that exercise can play a protective role in the development and progression of heart failure and improve cardiac function through various mechanisms, such as attenuating cardiac fibrosis, reducing inflammation, and regulating mitochondrial metabolism. Further investigation into the role and underlying mechanisms of exercise in heart failure may uncover novel therapeutic targets for the prevention and treatment of heart failure.

The Vectorcardiogram Characteristic and Its Predictive Value for Reduced Left Ventricular Ejection Fraction of Children with Duchenne Muscular Dystrophy.

Background: The prognosis of Duchenne muscular dystrophy (DMD) is poor once it develops to the stage of cardiac impairment. Recent studies have demonstrated that electrocardiogram (ECG), which consists of general ECG and vectorcardiogram (VCG), retains an extremely powerful role in the assessment of patients with reduced left ventricular (LV) systolic dysfunction. However, data regarding VCG recordings in DMD and its prognostic value for reduced left ventricular ejection fraction (LVEF) of DMD have never been reported. This study aims to describe the characteristics of VCG in children with DMD and to explore the predictive value of VCG for reduced LVEF in children with DMD. Methods: A total of 306 patients with a known diagnosis of DMD confirmed by the genetic test were retrospectively enrolled at our hospital between August 2018 and August 2022. This resulted in a total study group of 486 VCG recordings. Among them, 75 DMD patients who underwent cardiac magnetic resonance (CMR) later after one year follow-up were prospectively enrolled. The trend of VCG parameters of DMD patients across the different age span were compared with age-matched normal children. Concordance statistic analysis was further performed to assess the validity of VCG parameters in predicting the occurrence of reduced LVEF in patients with DMD. Results: DMD patients have a significantly higher heart rate, R waves in V1, QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) than normal children. Concordance statistic (C-statistic) showed an area under the curve of quadrant IV in the sagittal plane of baseline was 0.704. The receiver operating characteristic (ROC) curve shows that quadrant IV in the sagittal plane of 7.57% was the optimal cutoff with a sensitivity of 53.3% and a specificity of 88.3% for predicting reduced LVEF in DMD patients. Conclusions: Our study firstly showed that QRS loop percentage in the right anterior quadrant in the horizontal plane (horizontal quadrant II) and QRS loop percentage in the anterior superior quadrant in the sagittal plane (sagittal quadrant IV) could be abnormal in DMD boys as early as before 5 years old. Evaluation of the myocardium by VCG in the early age to predict possible cardiac systolic dysfunction may have important implications for the ongoing management of DMD boys.

Correlation of head injury with ECG and echo changes.

Background: Abnormal electrocardiogram (ECG) findings can be seen in traumatic brain injury (TBI) patients. ECG may be an inexpensive tool to identify patients at high risk for developing cardiac dysfunction after TBI. This study aimed to examine abnormal ECG findings after isolated TBI and their association with true cardiac dysfunction based on echocardiogram. Methods: This prospective observational study examined the data from adult patients with isolated and non-operated TBI between 2020 and 2021. Patients aged <18 years and >65 years with and presence of extracranial injuries including orthopedic, chest, cardiac, abdominal, and pelvis, pre-existing cardiac disease, patients who have undergone cardiothoracic surgery, with inotrope drugs, acute hemorrhage, and brain death were excluded from the study. Results: We examined data from 100 patients with isolated TBI who underwent ECG and echocardiographic evaluation. ECG changes among 53% of mild cases showed a heart rate of 60-100/min, and 2% of cases showed more than 100/min. Prolonged pulse rate (PR) interval was observed in 8%, 11%, and 16% of mild, moderate, and severe cases, while no changes in PR interval were observed in 65% of cases. A prolonged QRS pattern was observed in 5%, 7%, and 15% of mild, moderate, and severe cases. A normal QRS complex was observed in 71% of cases. Prolonged QTc was observed in 3%, 10%, and 15% of cases in mild, moderate, and severe cases, respectively. Conclusion: Repolarization abnormalities, but not ischemic-like ECG changes, are associated with cardiac dysfunction after isolated TBI. 12-lead ECG may be an inexpensive screening tool to evaluate isolated TBI patients for cardiac dysfunction.

Comparative Study Between the Effects of High Doses of Rosuvastatin and Atorvastatin on Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Most studies reported that treating ST-Elevation Myocardial Infarction (STEMI) patients with high doses of rosuvastatin or atorvastatin could improve left ventricular remodeling and cardiac function. PURPOSE: The current study compared the impact of high doses of rosuvastatin and atorvastatin on hypertrophy, fibrosis markers, serum inflammatory markers, and left ventricular function in STEMI patients after primary percutaneous coronary intervention (PCI). METHOD: After primary PCI, eighty STEMI patients were randomized to receive either 20 mg of rosuvastatin (n = 40) or 40 mg of atorvastatin (n = 40) once daily for 3 months. Soluble Suppression of Tumorigenicity-2 (sST2), Matrix Metalloproteinase-9 (MMP9), C-Reactive Protein (CRP), lipid parameters, liver enzymes, and echocardiographic parameters were assessed for the two groups at baseline and after 3 months. RESULTS: After 3 months of treatment, a statistically significant reduction was observed in the rosuvastatin group regarding the levels of CRP (16 ± 6 vs. 20 ± 10 mg/L, P = 0.024) and MMP9 (104 ± 33 vs. 130 ± 42 ng/L, P = 0.003) compared with the atorvastatin group. The median percentage decrease in sST2 level in the rosuvastatin group was higher (6.1%) than in the atorvastatin group (2.3%) after 3 months of treatment. Also, in the rosuvastatin group, LVEF was significantly increased (48.5 ± 9 vs. 43.5 ± 11%, P = 0.029), while LVEDV and LVESV were significantly decreased compared to those of the atorvastatin group (101 [81/135] vs. 134 [100/150] ml, P = 0.041) (53 [37/75] vs. 73 [52/92] ml, P = 0.033), respectively. CONCLUSION: High-intensity rosuvastatin was superior to high-intensity atorvastatin in reducing the inflammatory response and myocardial fibrosis, thus improving ventricular remodeling and cardiac function better in STEMI patients. TRIAL REGISTRATION: This randomized controlled trial was registered on October 11, 2022, on ClinicalTrials.gov under registration number: NCT05895123 "retrospectively registered".

Dapagliflozin in heart failure and type 2 diabetes: Efficacy, cardiac and renal effects, safety.

BACKGROUND: Heart failure (HF), especially HF with reduced ejection fraction (HFrEF), presents complex challenges, particularly in the aging population where it often coexists with type 2 diabetes mellitus (T2DM). AIM: To analyze the effect of dapagliflozin treatment on cardiac, renal function, and safety in patients with HFrEF combined with T2DM. METHODS: Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this study. The propensity score matching method was used, and a total of 102 eligible samples were scaled. The clinical efficacy of the two groups was evaluated at the end of the treatment, comparing the results of blood glucose, insulin, cardiac function, markers of myocardial injury, renal function indexes, and 6-min walk test (6MWT) before and after the treatment. We compared the occurrence of adverse effects on the treatment process of the two groups of patients. The incidence of adverse outcomes in patients within six months of treatment was counted. RESULTS: The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group (P = 0.013). After treatment, the pancreatic beta-cell function index, left ventricular ejection fraction, and glomerular filtration rate of patients in the study group were significantly higher than control group (P < 0.001), while their fasting plasma glucose, 2-h postprandial glucose, glycosylated hemoglobin, insulin resistance index, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, cardiac troponin I, creatine kinase-MB, N-terminal pro b-type natriuretic peptide, serum creatinine, and blood urea nitrogen were significantly lower than those of the control group. After treatment, patients in the study group had a significantly higher 6MWT than those in the control group (P < 0.001). Hypoglycemic reaction (P = 0.647), urinary tract infection (P = 0.558), gastrointestinal adverse effect (P = 0.307), respiratory disturbance (P = 0.558), and angioedema (P = 0.647) were not statistically different. There was no significant difference between the incidence of adverse outcomes between the two groups (P = 0.250). CONCLUSION: Dapagliflozin significantly enhances clinical efficacy, cardiac and renal function, and ambulatory capacity in patients with HFrEF and T2DM without an increased risk of adverse effects or outcomes.

Effects of concurrent training and N-acetylcysteine supplementation on cardiac remodeling and oxidative stress in middle-aged spontaneously hypertensive rats.

BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.

Empagliflozin combined with sacubitril/valsartan in hypertensive patients with heart failure: a retrospective study of efficacy and effect on blood pressure variability and cardiac function.

OBJECTIVE: To evaluate the efficacy of empagliflozin combined with sacubitril/valsartan in treating hypertensive patients with heart failure (HF), focusing on its effects on blood pressure variability (BPV) and cardiac function. METHODS: This retrospective study included 101 patients with hypertension and heart failure with reduced ejection fraction treated at Baoji High-Tech Hospital from October 2021 to October 2023. Patients were divided into two groups: an observation group (n=51), treated with both empagliflozin and sacubitril/valsartan, and a control group (n=50), treated with sacubitril/valsartan alone. We compared the therapeutic effects, BPV (including 24-hour, daytime, and nighttime systolic and diastolic BPV), cardiac function indicators, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) before and after treatment, and the incidence of adverse reactions between the groups. Independent risk factors affecting treatment efficacy were also analyzed. RESULTS: The total effective rate of treatment in the observation group was significantly higher than in the control group (P<0.05). Both groups showed reductions in daytime and nighttime systolic and diastolic BPV after treatment, with the observation group displaying more pronounced improvements (all P<0.05). Enhancements in cardiac ultrasound measurements, NT-proBNP levels, and cTnI levels were more significant in the observation group compared to the control group post-treatment (both P<0.05). There was no significant difference in the incidence of adverse reactions during treatment between the two groups (P>0.05). Age and comorbid diabetes were identified as independent risk factors for poor prognosis, while treatment with empagliflozin combined with sacubitril/valsartan was a protective factor. CONCLUSION: Empagliflozin combined with sacubitril/valsartan significantly enhances treatment efficacy in hypertensive patients with heart failure, effectively improves cardiac function and BPV, and demonstrates good safety.

Vericiguat on C-reactive Protein Level and Prognosis in Patients with Hypertensive Heart Failure.

INTRODUCTION: Hypertensive heart failure (HHF) has a high incidence and poor prognosis. AIM: This article evaluated the efficacy and safety of Vericiguat in HHF and analyzed the relationship between C-reactive protein (CRP) levels and patient prognosis. METHODS: 110 HHF patients were divided into Placebo and Vericiguat groups. Cardiac function was assessed by echocardiography and 6-minute walk test (6MWT). Blood samples were collected to detect the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), endothelin (ET-1), nitric oxide (NO), and CRP. RESULTS: Left ventricular end systolic diameter (LVESD) and left ventricular end diastolic dimension (LVEDD) were reduced, the left ventricular ejection fraction (LVEF) and 6MWT were increased, and the serum levels of NT-proBNP, cTnI, ET-1, NO, and CRP were decreased in Vericiguat group as against Placebo group; The total effective rate was 76.4% in Placebo group and 92.7% in Vericiguat group (P < 0.05). The adverse reaction rate was 10.9% and 9.1% (P > 0.05). The proportion of persons with poor prognosis and no improvement of cardiac function in patients with highly expressed CRP before treatment was higher as against patients with low expression of CRP (P < 0.05). Highly expressed CRP is an independent risk factor for poor prognosis. CONCLUSION: Vericiguat is safe and effective in improving cardiac function in HHF patients.