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

Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of "harmful hyperactivity and responding inhibition" is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to "inhibition and hyperactivity becoming harmful". The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should "nourish heart Qi, regulate the five Zang-organs, so as to restrain excess". The middle-stage treatment should "active blood, resolve phlegm, dispel pathogen, and eliminate turbidity", so as to alleviate hyperactivity. The late-stage treatment should "warm Yang, replenish Qi, active blood, and excrete water". Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.
Humans ; Ferroptosis ; Lipid Peroxides ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Chronic Disease ; Iron ; Water

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Child ; Adult ; Humans ; Antimalarials/pharmacology* ; Cardiovascular Diseases/drug therapy* ; Artemisinins/pharmacology* ; Quinolines ; Malaria, Cerebral/drug therapy* ; Heart Failure/drug therapy* ; Arrhythmias, Cardiac/drug therapy*

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), β-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-β1, α-SMA, Wnt3a, and β-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.
Mice ; Animals ; Transforming Growth Factor beta1/metabolism* ; Matrix Metalloproteinase 2/metabolism* ; beta Catenin/metabolism* ; Matrix Metalloproteinase 3/therapeutic use* ; Powders ; Ventricular Remodeling ; Stroke Volume ; Ventricular Function, Left ; Myocardial Infarction/drug therapy* ; Myocardium/pathology* ; Heart Failure/metabolism* ; Collagen/metabolism* ; Creatine Kinase ; Fibrosis

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.
Rats ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats, Sprague-Dawley ; TOR Serine-Threonine Kinases/metabolism* ; Heart Failure/drug therapy* ; Autophagy ; Fibrosis

This study aims to systematically review the efficacy and safety of different traditional Chinese medicine injections combined with conventional treatment for patients with post-acute myocardial infarction heart failure. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library with the time interval from inception to May 13, 2023. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Network Meta-analysis was then performed in RevMan 5.3 and Stata 15.1. A total of 68 RCTs involving 11 traditional Chinese medicine injections and 5 995 patients were included. The results were explained based on the surface under the cumulative ranking curve(SUCRA).(1) In terms of reducing major adverse cardiovascular event(MACE), the therapies followed the trend of Xinmailong Injection+conventional treatment(83.8%) > Yiqi Fumai Injection+conventional treatment(57.1%) > Xuebijing Injection+conventional treatment(56.6%) > Shenmai Injection+conventional treatment(53.1%) > Shenfu Injection+conventional treatment(45.3%) > conventional treatment(4.0%).(2) In terms of increasing left ventricular ejection fraction(LVEF), the therapies followed the trend of Yiqi Fumai Injection+conventional treatment(84.0%) > Shenmai Injection+conventional treatment(69.6%) > Shenfu Injection+conventional treatment(62.7%) > Xinmailong Injection+conventional treatment(61.6%) > Shuxuening Injection+conventional treatment(54.8%) > Shenqi Fuzheng Injection+conventional treatment(46.7%) > Shengmai Injection+conventional treatment(45.9%) > Breviscapine Injection+conventional treatment(39.9%) > Danhong Injection+conventional treatment(38.8%) > Huangqi Injection+conventional treatment(38.7%) > conventional treatment(7.3%).(3) In terms of reducing B-type natriuretic peptide(BNP), the therapies followed the trend of Xinmailong Injection+conventional treatment(98.6%) > Shenmai Injection+conventional treatment(57.7%) > Shenfu Injection+conventional treatment(52.5%) > Shengmai Injection+conventional treatment(30.1%) > conventional treatment(11.0%).(4) In terms of reducing cardiac troponin Ⅰ(cTnⅠ), the therapies followed the trend of Shenmai Injection+conventional treatment(92.3%) > Yiqi Fumai Injection+conventional treatment(61.5%) > Shenfu Injection+conventional treatment(51.2%) > Shengmai Injection+conventional treatment(48.1%) > Xinmailong Injection+conventional treatment(26.6%) > conventional treatment(20.3%).(5) In terms of reducing high-sensitivity C-reactive protein(hs-CRP), the therapies followed the trend of Shenmai Injection+conventional treatment(79.9%) > Xinmailong Injection+conventional treatment(68.1%) > Shenfu Injection+conventional treatment(63.1%) > Xuebijing Injection+conventional treatment(56.7%) > Shengmai Injection+conventional treatment(51.1%) > Shenqi Fuzheng Injection+conventional treatment(42.8%) > Huangqi Injection+conventional treatment(34.7%) > conventional treatment(3.5%).(6) A total of 22 RCTs reported the occurrence of adverse reactions, mainly involving the damage of the circulatory system, digestive system, and coagulation function. The current evidence suggested that Xinmailong Injection+conventional treatment may have the best therapeutic effect in reducing MACE and BNP; Yiqi Fumai Injection+conventional treatment may be the best in increasing LVEF; Shenmai Injection+conventional treatment may be the best in reducing cTnI and hs-CRP. The safety needs further quantitative research and analysis. However, more high-quality RCT is required to validate the above conclusions due to limitations in the quality and quantity of the included studies.
Humans ; Medicine, Chinese Traditional ; Stroke Volume ; Network Meta-Analysis ; C-Reactive Protein ; Ventricular Function, Left ; Drugs, Chinese Herbal/adverse effects* ; Myocardial Infarction/drug therapy* ; Heart Failure/drug therapy*

Chronic heart failure(CHF) is a comprehensive clinical syndrome caused by multiple factors that result in structural and/or functional abnormalities of the heart, leading to impaired ventricular contraction and/or relaxation functions. This medical condition represents the final stage of various cardiovascular diseases. In the treatment of CHF, multiple clinical studies have demonstrated the benefits of using traditional Chinese medicine(TCM) to control oxidative stress, inflammation, and apoptosis, thereby delaying ventricular remodeling and reducing myocardial fibrosis. In this study, common TCM syndromes in the diagnosis and treatment of CHF in recent years were reviewed and summarized. Five common treatment methods including benefiting Qi and activating blood circulation, enhancing Qi and nourishing Yin, warming Yang for diuresis, eliminating phlegm and dampness, rescuing from collapse by restoring Yang, and corresponding classic prescriptions in prevention and treatment of CHF were concluded under the guidance of TCM syndrome differentiation thinking. Meanwhile, research progress on the modern pharmacological effects of these classic prescriptions was systematically discussed, so as to establish a unique treatment system for CHF by classic prescriptions under the guidance of TCM syndrome differentiation theory and provide innovative diagnosis and treatment strategies for clinical CHF.
Humans ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Chronic Disease ; Syndrome