OBJECTIVE: To explore the correlation between albumin (Alb) combined with diuretic treatment and the mortality risk of septic patients with pre-existing congestive heart failure based on the United States Critical Care Medical Information Database-IV (MIMIC-IV), and to conduct the external validation. METHODS: A retrospective cohort study was conducted. The clinical data of septic patients with pre-existing congestive heart failure admitted to the intensive care unit (ICU) from 2008 to 2019 in the MIMIC-IV 2.0 were extracted, including demographic characteristics, comorbidities, laboratory indicators on the first day of ICU admission, severity of illness, treatment measures, etc. For external validation, clinical data were collected from septic patients with pre-existing congestive heart failure admitted to the ICU of the Second People's Hospital of Shenzhen from October 2022 to December 2023. The patients were divided into Alb alone group and Alb combined with diuretic group. The ICU mortality was defined as the primary outcome event, and the 30-day and 60-day mortality were defined as the secondary outcomes. Multivariate Cox proportional hazard regression analysis was conducted to investigate the relationship between Alb combined with diuretic treatment and the mortality risk of ICU and 30 days in septic patients with pre-existing congestive heart failure, and subgroup analysis was performed. Kaplan-Meier survival curve was plotted to compared the 60-day cumulative survival rate between the Alb alone group and Alb combined with diuretic group. RESULTS: (1) Analysis results of data from MIMIC-IV: a total 1 754 patients were enrolled, of which 378 in the Alb alone group, and 1 376 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients in the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.11% (263/1 376) vs. 30.42% (115/378), 30-day mortality: 18.90% (260/1 376) vs. 32.54% (123/378), 60-day mortality: 24.49% (337/1 376) vs. 39.15% (148/378), all P < 0.05]. Based on the multivariate Cox proportional hazard regression adjusted models considering demographic characteristics, comorbidities, laboratory indicators, severity of illness, and treatment measures, it was shown that the use of Alb combined with diuretic was significantly associated with a reduced risk death of ICU and 30 days [ICU mortality risk: hazard ratio (HR) = 0.597, 95% confidence interval (95%CI) was 0.460-0.774, P < 0.001; 30-day mortality risk: HR = 0.557, 95%CI was 0.433-0.716, P < 0.001]. Subgroup analysis revealed that after adjusting for variables, regardless of gender, age, and whether or not patients had comorbidities such as hypertension, diabetes, severe liver disease, acute renal insufficiency, and sequential organ failure assessment (SOFA) score, the ICU mortality risk was significantly reduced in patients treated with Alb combined with diuretic (all HR < 1, P < 0.05), with no interaction observed (all P > 0.05). Kaplan-Meier survival curve showed the 60-day cumulative survival rate of patients in the Alb combined with diuretic group was significantly higher than that in the Alb alone group (Log-rank test: χ ² = 49.62, P < 0.05). (2) External validation: a total of 385 patients were enrolled, of which 144 in the Alb alone group, and 241 in the Alb combined with diuretic group. Compared with the Alb alone group, the patients of the Alb combined with diuretic group had significantly lower ICU, 30-day, and 60-day mortality [ICU mortality: 19.92% (48/241) vs. 31.25% (45/144), 30-day mortality: 19.09% (46/241) vs. 28.47% (41/144), 60-day mortality: 24.07% (58/241) vs. 34.03% (49/144), all P < 0.05]. The results of multivariate Cox proportional hazard regression analysis, subgroup analysis, and Kaplan-Meier survival curve analysis were consistent with the data analysis of the MIMIC-IV database. CONCLUSIONS Combination therapy of Alb and diuretic was associated with reduced mortality risk in septic patients with pre-existing congestive heart failure.
Humans ; Heart Failure/mortality* ; Retrospective Studies ; Sepsis/drug therapy* ; Intensive Care Units ; Diuretics/therapeutic use* ; Male ; Female ; Aged ; Middle Aged ; Proportional Hazards Models ; Hospital Mortality

INTRODUCTION: We investigated the factors associated with readmission in patients with congestive heart failure (HF) receiving long-term administration of tolvaptan (TLV) to support treatment decisions for HF. METHODS: This retrospective cohort study included 181 patients with congestive HF who received long-term administration of TLV. Long-term administration of TLV was defined as the administration of TLV for 60 days or longer. The outcome was a readmission event for worsening HF within 1 year after discharge. Significant factors associated with readmission were selected using multivariate analysis. To compare the time to readmission using significant factors extracted in a multivariate analysis, readmission curves were constructed using the Kaplan-Meier method and analysed using the log-rank test. RESULTS: The median age was 78 years (range, 38-96 years), 117 patients (64.6%) were males, and 77 patients (42.5%) had a hospitalisation history of HF. Readmission for worsening HF within 1 year after long-term TLV treatment occurred in 62 patients (34.3%). In the multivariate analysis, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 (odds ratio, 3.22; 95% confidence interval, 1.661-6.249; P = 0.001) was an independent significant factor. When eGFR at discharge was divided into two groups (eGFR < 30 vs. eGFR ≥ 30), readmission rates within 1 year were 53.3% vs. 25.4%, respectively ( P = 0.001). CONCLUSION We revealed that eGFR was strongly associated with readmission in patients with HF who received long-term administration of TLV. Furthermore, we showed that eGFR is an important indicator in guiding treatment of HF in patients receiving TLV.
Humans ; Tolvaptan/therapeutic use* ; Heart Failure/drug therapy* ; Male ; Female ; Patient Readmission/statistics & numerical data* ; Aged ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Glomerular Filtration Rate ; Adult ; Antidiuretic Hormone Receptor Antagonists/therapeutic use* ; Risk Factors ; Kaplan-Meier Estimate ; Multivariate Analysis

Myocardial infarction(MI) is a cardiovascular disease with high disability and mortality rates in clinical practice, which can subsequently develop into complications such as heart failure(HF) or cardiac rupture. Proteomics can track changes in relevant functional molecules during the occurrence and progression of diseases from an overall, molecular, systematic, and flux perspectives. Utilizing proteomic techniques to deeply explore the functional targets, molecular mechanisms, and network effects of MI and HF can aid in early diagnosis, early warning, and drug treatment of these diseases. In recent years, significant progress has been made in the prevention and treatment of HF following MI using traditional Chinese medicine(TCM), particularly in elucidating the complex mechanisms of action through proteomic techniques. This article systematically reviewed research on the intervention mechanisms of TCM compound prescriptions and their active ingredients in HF after MI, and explored related in vivo pathways. Additionally, it discussed the role of proteomics in protein biomarker discovery, post-translational modifications of proteins, protein-protein interactions, spatial proteomics, and more, with the aim of advancing the deep application of proteomic techniques in the prevention and treatment of cardiovascular diseases with TCM.
Humans ; Proteomics ; Myocardial Infarction/drug therapy* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal

Humans ; Heart Failure/drug therapy* ; Diabetes Mellitus, Type 2/drug therapy* ; Glucose ; Sodium

OBJECTIVE: To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF). METHODS: Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting. RESULTS: The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs. CONCLUSIONS STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.
Rats ; Animals ; Matrix Metalloproteinase 2/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; RNA-Seq ; Transcriptome/genetics* ; Heart Failure/drug therapy* ; Collagen ; Collagen Type I/metabolism* ; Fibrosis ; Myocardium/pathology*

OBJECTIVE: To explore the cardioprotective effects of astragaloside IV (AS-IV) in heart failure (HF). METHODS: PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, Wanfang Database, Chinese Bio-medical Literature and Retrieval System (SinoMed), China Science and Technology Journal Database (VIP), and China National Knowledge Infrastructure (CNKI) were searched from inception to November 1, 2021 for animal experiments to explore AS-IV in treating HF in rats or mice. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular weight-to-body weight (LVW/BW) and B-type brain natriuretic peptide (BNP) were recorded. The qualities of included studies were assessed by the risk of bias according to the Cochrane handbook. Meta-analysis was performed using Stata 13.0. RESULTS: Twenty-one articles involving 558 animals were considered. Compared with the control group, AS-IV improved cardiac function, specifically by increasing LVEF (mean difference (MD)=6.97, 95% confidence interval (CI)=5.92 to 8.03, P<0.05; fixed effects model) and LVFS (MD=7.01, 95% CI=5.84 to 8.81, P<0.05; fixed effects model), and decreasing LVEDD (MD=-4.24, 95% CI=-4.74 to -3.76, P<0.05; random effects model) and LVESD (MD=-4.18, 95% CI=-5.26 to -3.10, P<0.05; fixed effects model). In addition, the BNP and LVW/BW levels were decreased in the AS-IV treatment group (MD=-9.18, 95% CI=-14.13 to -4.22, P<0.05; random effects model; MD=-1.91, 95% CI=-2.42 to -1.39, P<0.05; random effects model). CONCLUSIONS AS-IV is a promising therapeutic agent for HF. However, this conclusion needs to be clinically validated in the future.
Animals ; Mice ; Rats ; Stroke Volume ; Ventricular Function, Left ; Heart Failure/drug therapy* ; Natriuretic Peptide, Brain

Humans ; Iron/therapeutic use* ; Heart Failure/drug therapy* ; Dietary Supplements

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.
Humans ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Macrophages ; Drugs, Chinese Herbal/therapeutic use*

Shenqi Pills, first recorded in Essentials from the Golden Cabinet(Jin Kui Yao Lue) from ZHANG Zhong-jing in Han dynasty, have the effect of warming and tonifying the kidney Qi and are mainly used for the treatment of insufficiency of kidney Qi and kidney Yang. According to modern medicine, kidney Qi involves heart function, kidney function, immune function, and so on. The clinical indications of Shenqi Pills include kidney deficiency, abnormal fluid, and abnormal urination, and the last one is classified into little urine, much urine, and dysuria. In clinical settings, Shenqi Pills can be applied for the treatment of heart failure, renal failure, cardiorenal syndrome, and diuretic resistance, as well as endocrine, urological, orthopedic, and other chronic degenerative diseases. Shenqi Pills are ideal prescriptions for the weak constitution and emergency treatment. It is of great value and significance to carry out in-depth research on the connotation of the classic articles by integrating TCM and western medicine based on "pathogenesis combined with pathology and drug properties combined with pharmacology".
Humans ; Cardio-Renal Syndrome/drug therapy* ; Diuretics/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/drug therapy* ; Critical Care