[Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure].

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

Injection of YiQiFuMai powder protects against heart failure via inhibiting p38 and ERK1/2 MAPKs activation.

CONTEXT: Injection of YiQiFuMai (YQFM) powder, a modern Chinese plant-derived medical preparation, has a therapeutic effect in heart failure (HF). However, its therapeutic mechanism remains largely unknown. OBJECTIVE: To investigate the molecular mechanisms of YQFM in HF. MATERIALS AND METHODS: Kinase inhibition profiling assays with 2 mg/mL YQFM were performed against a series of 408 kinases. In addition, the effects of kinase inhibition were validated in cardiomyocyte cell line H9c2. In vivo, HF with reduced ejection fraction (HFrEF) was induced by permanent left anterior descending (LAD) coronary artery ligation for 6 weeks in male Sprague-Dawley rats. Then, HFrEF mice were treated with 0.46 g/kg YQFM or placebo once a day for 2 weeks. Echocardiography, immunohistochemistry, histological staining and Western blotting analysis were performed to assess the myocardial damage and molecular mechanisms. RESULTS: Kinase inhibition profiling analysis demonstrated that mitogen-activated protein kinases (MAPKs) mediated the signalling cascades of YQFM during HF therapy. Meanwhile, p38 and extracellular signal-regulated kinases (ERK1/2) were inhibited after YQFM treatment in H9c2 cells. In rats, the control group had lower left ventricular ejection fraction (LVEF) at 37 ± 1.7% compared with the YQFM group at 54 ± 1.1% (p < 0.0001). Cardiac fibrosis levels in control group rats were significantly higher than YQFM group (30.5 ± 3.0 vs. 14.1 ± 1.0, p < 0.0001). CONCLUSIONS: Our collective in vitro and in vivo experiments demonstrated that YQFM improves left ventricular (LV) function and inhibits fibrosis in HFrEF rats by inhibiting MAPK signalling pathways.

Exercise and Urtica Dioica extract ameliorate mitochondrial function and the expression of cardiac muscle Nuclear Respiratory Factor 2 and Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha in STZ-induced diabetic rats.

INTRODUCTION: Diabetes mellitus can affect and disrupt the levels of PGC1α and NRF2 proteins in the mitochondrial biogenesis pathway. Considering the anti-diabetic properties of Urtica Dioica extract and exercise, this study aimed to investigate the beneficial effects of Urtica Dioica extract and endurance activity on PGC1α and NRF2 protein levels in the streptozotocin-induced diabetic rat heart tissue. MATERIALS AND METHODS: 58 male Wistar rats were divided into five groups (N = 12) including: healthy control (HC), diabetes control (DC), diabetes Urtica Dioica (D-UD), diabetes exercise training (DT), and diabetes exercise training Urtica Dioica (DT-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the induction of diabetes, the rats were stimulated to carry out the exercise (moderate intensity/5day/week) and the gavage of UD extract (50 mg/kg/day) was administered to the rats for six weeks. In this study, the western blotting method was used to measure the levels of PGC1α and NRF2 proteins. Moreover, cardiography was used to evaluate the functional parameters of the heart (ejection fraction & fractional shortening). Finally, the bioluminescence and ELISA methods were used to determine the content of adenosine triphosphate and citrate synthase. RESULTS: The cardiac function parameters, the mitochondrial ATP and the CS content in DC group mice were impaired in comparison with the other study groups and showed a decreasing trend (P < 0.001). The treatment with EX + UD extract was able to minimize the rate of these disorders and acted as a protector of mitochondrial function. There were significant differences in the expression levels of NRF2 (F = 17.7, P = 0.001) and PGC-1α (F = 43.7, P = 0.001) mitochondrial proteins among the different groups. The levels of these proteins were significantly reduced in the DC group in comparison with the HC group (P < 0.001). The treatment with EX or UD extract increased the expression of PGC-1α and NRF2 proteins in the heart muscle of animals in the DT and D-UD groups in comparison with the DC group (P < 0.05). Moreover, the expression of these proteins was more pronounced in the DT-UD group. There was not a significant difference between the DT-UD group and the HC group regarding the expression of these proteins (P > 0.05). CONCLUSIONS: The results of this study showed that treatment with EX and UD extract could treat the disorders which were caused by diabetes in the parameters of cardiac function. Moreover, it was able to improve the expression of the levels of proteins which were involved in mitochondrial biogenesis and its function. Finally, this kind of treatment could attract more attention to the roles of EX and UD extract in the prevention of cardiovascular complications in future studies.

Attenuation of ischemia-reperfusion injury by intracoronary chelating agent administration.

Ischemia-reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and thus abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. We investigated the efficacy of intracoronary ethylenediaminetetraacetic acid (EDTA) administration as an adjunctive treatment to coronary intervention to reduce IR injury in a swine model. We occluded the left anterior descending artery for 1 h. From the time of reperfusion, we infused 50 mL of EDTA-based chelating agent via the coronary artery in the EDTA group and normal saline in the control group. IR injury was identified by myocardial edema on echocardiography. Tetrazolium chloride assay revealed that the infarct size was significantly lower in the EDTA group than in the control group, and the salvage percentage was higher. Electron microscopy demonstrated that the mitochondrial loss in the cardiomyocytes of the infarcted area was significantly lower in the EDTA group than in the control group. Echocardiography after 4 weeks showed that the remodeling of the left ventricle was significantly less in the EDTA group than in the control group: end-diastolic dimension 38.8 ± 3.3 mm vs. 43.9 ± 3.7 mm (n = 10, p = 0.0089). Left ventricular ejection fraction was higher in the EDTA group (45.3 ± 10.3 vs. 34.4 ± 11.8, n = 10, respectively, p = 0.031). In a swine model, intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction.

Coenzyme Q10 in the Treatment of Heart Failure with Preserved Ejection Fraction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).

Signature network-based survey of the effects of a traditional Chinese medicine on heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Heart failure (HF) after myocardial infarction (MI) is one of the most common disabling and painful diseases. A traditional Chinese medicine (TCM) formula, Shengmaisan, is known as a multitarget medicine that is widely used clinically to treat heart failure (HF) in Asian countries. However, its mechanism has not been comprehensively demonstrated. AIM OF THE STUDY: To use a prediction network to figure out which disease link SMZ mainly alleviates in HF and find biomarkers related to myocardial fibrosis in the serum for clinical reference. MATERIALS AND METHODS: In this article, we collected a large amount of actual measurement data and our own proteomics data, along with the biomarkers of heart failure staging under study to establish a precise network. Then, we tested and verified the medicinal effect of SMZ in treatment of HF after MI by Measurement of left ventricular wall thickness and ejection fraction by echocardiography. Then we tested the serum level of the potential targets of SMZ predicting by the network we developed using ELISA. RESULTS: the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle increased after treating with SMZ. The serum level of EGFR and MAPK1 decreased in the groups treated with SMZ. CONCLUSION: SMZ can improve the cardiac function of rats with MI by increasing the cardiac ejection fraction and retarding the thinning of the anterior wall of the left ventricle. In addition, SMZ could delay heart failure mainly by inhibiting the progression of myocardial fibrosis through decreasing the EGFR and MAPK1 levels.

Impacts of Yangxin decoction on the expressions of MMP-9, CaN, NFAT3 and GATA4 in myocardial tissue of rats with chronic heart failure.

To investigate the impacts of Yangxin decoction on the expressions of matrix metalloproteinase 9 (MMP-9), calcineurin (CaN), T cell activated nuclear factor 3 (NFAT3) and zinc finger transcription factor 4 (GATA4) in myocardial tissue of rats with chronic heart failure (CHF). 50 healthy SD rats were randomly divided into the normal control group (n = 10) and the operation group (n = 40). After successful modeling, the rats were randomly divided into 4 groups. And they were treated with Yangxin decoctions of low concentration (1.5 g/kg), medium concentration (2.5 g/kg), high concentration (3.5 g/kg) and distilled water (for 4 weeks). The LVSP, SAP, DAP and LVEDP in Yangxin decoction treatment groups were significantly superior to the model group. The LVEF, LVIDd and LVIDs in Yangxin decoction treatment groups were significantly superior to the model group. The activity of CaN in each group treated with Yangxin decoction was significantly lower than that in the model group. The expression levels of MMP-9, NFAT3, GATA4 protein in each group treated with Yangxin decoction were significantly lower than that in the model group.. Yangxin decoction can significantly improve the cardiac function, reduce CaN activity, decrease the expression levels of MMP-9, NFAT3 and GATA4, inhibit CaN/NFAT3 signaling pathway, increase myocardial remodeling and protect myocardial tissue in rats with CHF.

The Effects of Sodium Phosphate Supplementation on the Cardiorespiratory System and Gross Efficiency during Exercise under Hypoxia in Male Cyclists: A Randomized, Placebo-Controlled, Cross-Over Study.

The main aim of this study was to evaluate the effects of six days of tri-sodium phosphate (SP) supplementation on the cardiorespiratory system and gross efficiency (GE) during exercise under hypoxia in cyclists. Twenty trained male cyclists received SP (50 mg·kg-1 of fat-free mass/day) or placebo for six days in a randomized, cross-over study, with a three-week washout period between supplementation phases. Before and after each supplementation phase, the subjects performed an incremental exercise test to exhaustion under normobaric hypoxia (FiO2 = 16%, ~2500 m). It was observed that short-term SP supplementation led to a decrease in heart rate, an increase in stroke volume, and an improvement in oxygen pulse (VO2/HR) during low and moderate-intensity exercise under hypoxia. These changes were accompanied by an increase in the serum inorganic phosphate level by 8.7% (p < 0.05). No significant changes were observed in serum calcium levels. GE at a given workload did not change significantly after SP supplementation. These results indicated that SP promotes improvements in the efficiency of the cardiorespiratory system during exercise in a hypoxic environment. Thus, SP supplementation may be beneficial for endurance exercise in hypoxia.

The Synergistic Effects of Astragalus mongholicus and Salvia miltiorrhiza on Coronary Heart Disease Identified by Network Pharmacology and Experiment.

BACKGROUND AND PURPOSE: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD. METHODS: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively. RESULTS: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05). CONCLUSION: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.

PUFA Supplementation and Heart Failure: Effects on Fibrosis and Cardiac Remodeling.

Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1-2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021.

Compound Danshen Dripping Pill inhibits doxorubicin or isoproterenol-induced cardiotoxicity.

Heart failure (HF) is the advanced heart disease with high morbidity and mortality. Compound DanShen Dripping Pill (CDDP) is a widely used Traditional Chinese Medicine for cardiovascular disease treatment. Herein, we investigated if CDDP can protect mice against doxorubicin (DOX) or isoprenaline (ISO)-induced HF. After 3 days feeding of normal chow containing CDDP, mice were started DOX or ISO treatment for 4 weeks or 18 days. At the end of treatment, mice were conducted electrocardiogram and echocardiographic test. Blood and heart samples were determined biochemical parameters, myocardial structure and expression of the related molecules. CDDP normalized DOX/ISO-induced heart weight changes, HF parameters and fibrogenesis. The DOX/ISO-impaired left ventricular ejection fraction and fractional shortening were restored by CDDP. Mechanistically, CDDP blocked DOX/ISO-inhibited expression of antioxidant enzymes and DOX/ISO-induced expression of pro-fibrotic molecules, inflammation and cell apoptosis. Additional DOX/ISO-impaired targets in cardiac function but protected by CDDP were identified by RNAseq, qRT-PCR and Western blot. In addition, CDDP protected cardiomyocytes against oxygen-glucose deprivation-induced injuries. Taken together, our study shows that CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment.

The effects of rice bran oil on left ventricular systolic function, cardiometabolic risk factors and inflammatory mediators in men with coronary artery disease: a randomized clinical trial.

BACKGROUND/OBJECTIVE: In the current study, we aimed to explore the effects of rice bran oil (RBO) in adjunct to conventional medical therapy on left ventricular ejection fraction (LVEF), cardiometabolic risk factors, and inflammatory mediators in male patients with coronary artery disease (CAD). SUBJECTS/METHODS: The present randomized controlled trial included 40 men diagnosed with CAD (mean age = 55.76 years) who were randomly allocated into two groups to receive either 30 grams per day of RBO (intervention group) or sunflower oil (control group) plus a standard diet for eight weeks. At the initial visit, demographic and anthropometric data and blood samples were collected. LVEF levels and serum concentrations of lipid profile, glucose, uric acid, hs-CRP, and TNF-α were investigated. RESULTS: A total of 37 participants completed the study (n = 18 in the intervention group, n = 19 in the control group). Analysis of covariance (ANCOVA) adjusted for baseline values, age and body mass index revealed that RBO significantly improved LVEF (51.34%) and reduced triglyceride (125.01 mg dl-1), blood sugar (110.4 mg dl-1), total cholesterol (123.01 mg dl-1) and low density lipoprotein (56.88 mg dl-1) levels compared to sunflower oil ((45.56%), (155.93 mg dl-1), (128.94 mg dl-1), (163.93 mg dl-1) and (83.79 mg dl-1), respectively) following a 8-week trial (P-values < 0.05). Additionally, the test demonstrated that RBO consuming patients had significantly lower levels of serum uric acid (4.60 mg dl-1), TNF-α (6.99 ng L-1) and hs-CRP (2.11 mg L-1) compared to the control group ((5.92 mg dl-1), (15.23 ng L-1), (4.47 mg L-1), respectively) (P-value < 0.05). However, no significant changes were found regarding weight, blood pressure or serum HDL levels throughout the trial. CONCLUSION: Consumption of 30 grams per day RBO within a standard diet could be considered an effective non-pharmacological approach in improving LVEF, cardiometabolic risk factors, and inflammatory state in CAD. However, future trials are recommended for more clarification.

Allyl Methyl Sulfide Preserved Pressure Overload-Induced Heart Failure Via Modulation of Mitochondrial Function.

BACKGROUND: Cardiovascular diseases are the leading cause of death globally, and they are causing enormous socio-economic burden to the developed and developing countries. Allyl Methyl Sulfide (AMS) is a novel cardioprotective metabolite identified in the serum of rats after raw garlic administration. The present study explored the cardioprotective effect of AMS on thoracic aortic constriction (TAC)-induced cardiac hypertrophy and heart failure model in rats. METHODS: Thoracic aortic constriction (TAC) by titanium ligating clips resulted in the development of pressure overload-induced cardiac hypertrophy and heart failure model. Four weeks prior to TAC and for 8 weeks after TAC, Sprague Dawley (SD) rats were administered with AMS (25 and 50 mg/kg/day) or Enalapril (10 mg/kg/day). RESULTS: We have observed AMS (25 and 50 mg/kg/day) intervention significantly improved structural and functional parameters of the heart. mRNA expression of fetal genes i.e., atrial natriuretic peptide (ANP), alpha skeletal actin (α-SA) and beta myosin heavy chain (ß-MHC) were reduced in AMS treated TAC hearts along with decrease in perivascular and interstitial fibrosis. AMS attenuated lipid peroxidation and improved protein expression of endogenous antioxidant enzymes i.e., catalase and manganese superoxide dismutase (MnSOD) along with electron transport chain (ETC) complex activity. AMS increased mitochondrial fusion proteins i.e., mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy protein (OPA1), and reduced fission protein i.e., dynamin-related protein 1 (DRP1). Preliminary study suggests that AMS intervention upregulated genes involved in mitochondrial bioenergetics in normal rats. Further, in-vitro studies suggest that AMS reduced mitochondrial reactive oxygen species (ROS), preserved mitochondrial membrane potential and oxygen consumption rate (OCR) in isoproterenol-treated cardiomyoblast. CONCLUSION: This study demonstrated that AMS protected cardiac remodelling, LV dysfunction and fibrosis in pressure overload-induced cardiac hypertrophy and heart failure model by improving endogenous antioxidants and mitochondrial function.

Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure.

BACKGROUND & AIMS: Heart failure (HF), as a major cardiac disease, is associated with considerable mortality, morbidities and poor quality of life. The aim of this study was to investigate the effect of l-arginine supplementation on cardiac outcomes and quality of life in patients with ischemic HF. METHODS: This double-blind randomized controlled clinical trial was conducted in 50 patients with ischemic HF. Patients were randomly assigned to receive either 3 gr/d l-arginine or placebo, for 10 weeks. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. RESULTS: The results showed significant improvements in ejection fraction (-6.5 ± 8.7 vs. -0.7 ± 7.8%, P = 0.037), left ventricular function (P = 0.043), diastolic dysfunction (P = 0.01) and marginally improvement in changes of left ventricular dimension during diastole (LVDd) (4 ± 6 vs. 0.3 ± 6.9 mm, P = 0.065) in the l-arginine compared to the placebo group. At the end of the study, physical aspect (5.7 ± 3.3 vs. 1.2 ± 6.1, P = 0.002) and total score (10 ± 6.7 vs. 4.1 ± 9.4, P = 0.011) of quality of life improved significantly in the l-arginine compared with the placebo group. Additionally, pre-to post-values of diastolic blood pressure, mean arterial pressure, LVDd, LV ejection fraction, left ventricular function, diastolic dysfunction as well as physical and total scores of quality of life improved significantly within the intervention, but not the placebo, group (all P < 0.05). CONCLUSION: This study showed that 3 gr/d l-arginine supplementation for 10 weeks could improve cardiac recovery and function, and quality of life in patients with HF. This study was registered at the Iranian Clinical Trial Registration Center (www.irct.ir) with IRCT20170202032367N4 code.

No Effects of Different Doses of New Zealand Blackcurrant Extract on Cardiovascular Responses During Rest and Submaximal Exercise Across a Week in Trained Male Cyclists.

Supplementation with anthocyanin-rich blackcurrant increases blood flow, cardiac output, and stroke volume at rest. It is not known whether cardiovascular responses can be replicated over longer timeframes in fed trained cyclists. In a randomized, double-blind, crossover design, 13 male trained cyclists (age 39 ± 10 years, V˙O2max 55.3 ± 6.7 ml·kg-1·min-1) consumed two doses of New Zealand blackcurrant (NZBC) extract (300 and 600 mg/day for 1 week). Cardiovascular parameters were measured during rest and submaximal cycling (65% V˙O2max) on day 1 (D1), D4, and D7. Data were analyzed with an RM ANOVA using dose (placebo vs. 300 vs. 600 mg/day) by time point (D1, D4, and D7). Outcomes from placebo were averaged to determine the coefficient of variation within our experimental model, and 95% confidence interval (CI) was examined for differences between placebo and NZBC. There were no differences in cardiovascular responses at rest between conditions and between days. During submaximal exercise, no positive changes were observed on D1 and D4 after consuming NZBC extract. On D7, intake of 600 mg increased stroke volume (3.08 ml, 95% CI [-2.08, 8.26]; d = 0.16, p = .21), cardiac output (0.39 L/min, 95% CI [-1.39, .60]; d = 0.14, p = .40) (both +2.5%), and lowered total peripheral resistance by 6.5% (-0.46 mmHg·min/ml, 95% CI [-1.80, .89]; d = 0.18, p = .46). However, these changes were trivial and fell within the coefficient of variation of our study design. Therefore, we can conclude that NZBC extract was not effective in enhancing cardiovascular function during rest and submaximal exercise in endurance-trained fed cyclists.

Selenium supplementation in patients with peripartum cardiomyopathy: a proof-of-concept trial.

BACKGROUND: We studied the efficacy and safety of selenium supplementation in patients who had peripartum cardiomyopathy (PPCM) and selenium deficiency. METHODS: We randomly assigned 100 PPCM patients with left ventricular ejection fraction (LVEF) < 45% and selenium deficiency (< 70 µg/L) to receive either oral Selenium (L-selenomethionine) 200 µg/day for 3 months or nothing, in addition to recommended therapy, in an open-label randomised trial. The primary outcome was a composite of persistence of heart failure (HF) symptoms, unrecovered LV systolic function (LVEF < 55%) or death from any cause. RESULTS: Over a median of 19 months, the primary outcome occurred in 36 of 46 patients (78.3%) in the selenium group and in 43 of 54 patients (79.6%) in the control group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.43-1.09; p = 0.113). Persistence of HF symptoms occurred in 18 patients (39.1%) in the selenium group and in 37 patients (68.5%) in the control group (HR 0.53; 95% CI 0.30-0.93; p = 0.006). LVEF < 55% occurred in 33 patients (71.7%) in the selenium group and in 38 patients (70.4%) in the control group (HR 0.91; 95% CI 0.57-1.45; p = 0.944). Death from any cause occurred in 3 patients (6.5%) in the selenium group and in 9 patients (16.7%) in the control group (HR 0.37; 95% CI 0.10-1.37; p = 0.137). CONCLUSIONS: In this study, selenium supplementation did not reduce the risk of the primary outcome, but it significantly reduced HF symptoms, and there was a trend towards a reduction of all-cause mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03081949.

Experimental model of congestive heart failure induced by transverse aortic constriction in BALB/c mice.

INTRODUCTION: Murine transverse aortic constriction (TAC) is a frequently used model of pressure overload-induced left ventricular (LV) remodeling. However, there is considerable variability in disease progression to overt heart failure (HF) development in the most commonly used strain of mice (i.e., C57BL/6J). Studies have shown that C57BL/6J mice are more resistant than BALB/c mice to congestive HF development following myocardial infarction or angiotensin II-induced hypertension. Therefore, we tested the hypothesis that BALB/c mice may be a better research model to study TAC-induced progressive HF. METHODS: Following sham or TAC surgery in both C57BL/6J (n = 29) and BALB/c (n = 32) mice, we evaluated cardiac dimensions and function by echocardiography at 2, 4, 8, and 12 weeks and monitored survival throughout the study. In a separate cohort of BALB/c mice, we repeated the study in the presence of the angiotensin converting enzyme inhibitor enalapril or a vehicle initiated 2 weeks post-TAC and administered for 6 weeks. At the end of the studies, we assessed the heart weight, lung weight, and plasma brain natriuretic peptide (BNP) concentration. RESULTS: Following comparable TAC, both C57BL/6J and BALB/c mice showed significant LV remodeling compared with the sham control mice. BALB/c mice progressively developed systolic dysfunction, LV dilation, lung congestion, and significant mortality, whereas C57BL/6J mice did not. In the separate cohort of BALB/c TAC mice, enalapril significantly reduced the heart weight, lung weight, and plasma BNP concentration and improved survival compared with the vehicle control. DISCUSSION: BALB/c mice uniformly developed congestive HF post-TAC. Enalapril was effective in improving survival and reducing lung congestion in this model. The data suggest that BALB/c mice may be a better research tool than C57BL/6J mice to study TAC-induced disease progression to HF and to evaluate novel therapies for the treatment of chronic HF with reduced ejection fraction.

Efficacy of Qishen Yiqi Drop Pill for Chronic Heart Failure: An Updated Meta-Analysis of 85 Studies.

BACKGROUND: Despite evidence for beneficial effects of Qishen Yiqi Drop Pill (QSYQ) on congestive heart failure, the majority of studies are based on insufficient sample sizes. The aim of this study was to evaluate the therapeutic effects of QSYQ using a meta-analysis approach. Methodology/Principal Findings. All relevant studies published before December 31, 2019, were identified by searches of various databases with key search terms. In total, 85 studies involving 8,579 participants were included. The addition of QSYQ to routine Western medicine increased 6-minute walking distance (SMD = 2.08, 95% CI: 1.72-2.44, p < 0.001), left ventricular ejection fraction (SMD = 1.05, 95% CI: 0.87-1.23, p < 0.001), and cardiac index (SMD = 1.44, 95% CI: 0.92-1.95, p < 0.001) and reduced brain natriuretic peptide (SMD = -2.28, 95% CI: -2.81 to -1.76, p < 0.001), N-terminal prohormone of brain natriuretic peptide (SMD = -2.49, 95% CI: -3.24 to -1.73, p < 0.001), left ventricular end-diastolic dimensions (SMD = -0.92, 95% CI: -1.25 to -0.59, p < 0.001), and left ventricular end-systolic dimensions (SMD = -0.55, 95% CI: -0.89 to -0.21, p < 0.001). The results were stable in subgroup analyses and sensitivity analyses. CONCLUSIONS: Our current meta-analysis indicated that QSYQ combined with Western therapy might be effective in CHF patients. Further researches are needed to identify which subgroups of CHF patients will benefit most and what kind of combination medicines work best.

Ginsenoside Rb1 Ameliorates Age-Related Myocardial Dysfunction by Regulating the NF-[Formula: see text]B Signaling Pathway.

Age-related myocardial dysfunction is a very large healthcare burden. Here, we aimed to investigate whether ginsenoside Rb1 (Rb1) improves age-related myocardial dysfunction and to identify the relevant molecular mechanism. Young mice and aged mice were injected with Rb1 or vehicle for 3 months. Then, their cardiac function was inspected by transthoracic echocardiography. Serum and myocardium tissue were collected from all mice for histological or molecular expression analyses, including aging-related proteins, markers relevant to fibrosis and inflammation, and markers indicating the activation of the nuclear factor-kappa B (NF-[Formula: see text]B) pathway. Compared with the control condition, Rb1 treatment significantly increased the ejection fraction percentage and significantly decreased the internal diameter and volume of the left ventricle at the end-systolic and end-diastolic phases in aged mice. Rb1 treatment reduced collagen deposition and collagen I, collagen III, and transforming growth factor-[Formula: see text]1 protein expression levels in aged hearts. Rb1 also decreased the aging-induced myocardial inflammatory response, as measured by serum or myocardial interleukin-6 and tumor necrosis factor-[Formula: see text] levels. Furthermore, Rb1 treatment in aged mice increased cytoplasmic NF-[Formula: see text]B but decreased nuclear NF-[Formula: see text]B, which indicated the suppression of the NF-[Formula: see text]B signaling pathway by regulating the translocation of NF-[Formula: see text]B. Rb1 could alleviate aging-related myocardial dysfunction by suppressing fibrosis and inflammation, which is potentially associated with regulation of the NF-[Formula: see text]B signaling pathway.