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Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the PII-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the PII-wave, thereby producing an antiarrhythmic effect.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chronic heart failure (CHF) is a severe consequence of cardiovascular disease, marked by cardiac dysfunction. Jin-Xin-Kang (JXK) is a traditional Chinese herbal formula used for the treatment of CHF. This formula consists of seven medicinal herbs, including Ginseng (Ginseng quinquefolium (L.) Alph.Wood), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge), Salvia miltiorrhiza (Salvia miltiorrhiza Bunge), Descurainiae Semen Lepidii Semen (Descurainia sophia (L.) Webb ex Prantl), Leonuri Herba (Leonurus japonicus Houtt.), Cinnamomi Ramulus (Cinnamomum cassia (L.) J.Presl), and Ilex pubescens (Ilex pubescens Hook. & Arn.). Its clinical efficacy has been validated through prospective randomized controlled studies. However, the specific mechanisms of action for this formula have yet to be elucidated. AIM OF THE STUDY: This study aimed to investigate the effect of JXK on mitochondrial function and its mechanism in the treatment of CHF. METHODS: JXK components were qualitatively analyzed using UPLC-Q-Orbitrap-MS. HF was induced in mice via transverse aortic constriction (TAC). After successful model establishment, lyophilized JXK-L (4.38 g/kg) and JXK-H (13.14 g/kg) were administered for 8 weeks. In vitro, hypertrophic myocardium was induced using angiotensin II (Ang II) for 48 hours, followed by JXK-L and JXK-H treatment. Network pharmacology and molecular docking techniques were used to predict the relevant targets of JXK. Cardiac function, serum markers, and histopathological changes were evaluated to assess cardiac function. Immunofluorescence of Tomm20, mitochondrial membrane potential, and ROS were measured to assess mitochondrial dysfunction. Protein expression of calcineurin (CaN) and Drp1 in the myocardium was assessed by Western blot analysis. RESULTS: We detected that the active components of JXK include terpenes, glycosides, flavonoids, amino acids, and alkaloids, among others. In mice with CHF, JXK improved cardiac function and reversed ventricular remodeling. Network pharmacology indicated that JXK can inhibit the calcium signaling pathway. The molecular docking results demonstrated that the active components of JXK effectively bind with CaN. Both in vitro and in vivo experiments confirmed that JXK regulated the CaN/Drp1 pathway and alleviated mitochondrial dysfunction. CONCLUSION: JXK can inhibit the CaN/Drp1 pathway to improve mitochondrial function, and consequently treat CHF.
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Objective: To evaluate the clinical efficacy, safety and compliance of quality nursing intervention in the treatment of chronic heart failure combined with respiratory tract infections. Methods: This was a retrospective study. One hundred and twenty patients with chronic heart failure combined with respiratory tract infections were recruited at Baoding No.1 Central Hospital from June 2021 to March 2023 and randomly divided into the control group (n=60) and the experimental group (n=60). Patients in the control group were given regular specialist care on the basis of basic treatment, while those in the experimental group were given a quality care intervention model. The differences in clinical efficacy, improvement time of symptoms after treatment, etc. between the two groups were compared and analyzed. Results: The response rate of the experimental group was 88%, which was significantly higher than that of the control group (73%), with a statistically significant difference (P=0.04). The time of fever reduction, cough subsidence and lung rales disappearance in the experimental group were significantly shorter than those of the control group, with statistically significant differences (P<0.05). The incidence of nursing related adverse events in the experimental group was 8%, which was lower than that of 23% in the control group, with a statistically significant difference(P=0.03). Conclusion: Quality nursing intervention is an effective treatment for patients with chronic heart failure combined with respiratory infections, boasting a variety of benefits such as reduced nursing risk, improved quality of nursing, and increased patient compliance and satisfaction. It contributes to rapid symptom improvement and significant clinical efficacy.
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Despite the presence of various signs of cardiac amyloidosis ("red flags"), the introduction into routine practice of new non-invasive diagnostic methods (Speckle Tracking technology using echocardiography, myocardial scintigraphy with technetium pyrophosphate, genetic testing, screening for free light chains of immunoglobulins to exclude AL-amyloidosis), which have high specificity and sensitivity, transthyretinic (ATTR) cardiomyopathy is still a difficult to diagnose disease, especially in the early stages when treatment is most effective. The article presents a clinical case of ATTR-amyloidosis with predominant heart damage, manifested by severe diastolic heart failure resistant to treatment. The timing, from the moment of the first episode of decompensation of heart failure to death, is 4 months, which confirms the rapid progression of severe biventricular dysfunction of the heart. Despite the presence of cardiac and extracardial "red flags" of ATTR-amyloidosis in the patient, the diagnosis was established at autopsy. The paper analyzes possible errors of early diagnosis at the outpatient and inpatient stages of patient management.
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Progresión de la Enfermedad , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/diagnóstico , Masculino , Resultado Fatal , Ecocardiografía/métodos , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/complicaciones , Neuropatías Amiloides Familiares/fisiopatología , Persona de Mediana Edad , Cardiomiopatías/diagnóstico , Cardiomiopatías/etiología , Cardiomiopatías/fisiopatologíaRESUMEN
AIM: To evaluate the efficacy and safety of the advanced technique for positioning the endocardial electrodes of a cardiac contractility modulation (CCM) device. MATERIALS AND METHODS: The CCM system was implanted in 100 patients, of which 60 CCM electrodes were positioned in the most optimal zones of myocardial perfusion, in particular, in the zone of the minor focal-scar/fibrotic lesion (the Summed Rest Score of 0 to 1-2, the intensity of the radiopharmaceutical at least 30%), and in 40 patients according to the standard procedure. Before the implantation of the CCM system, 60 patients underwent tomography (S-SPECT) of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest to determine the most optimal electrode positioning zones and 100 patients underwent transthoracic echocardiography at baseline and after 12 months to assess the effectiveness of surgical treatment. RESULTS: Improved ventricular electrode positioning technique is associated with the best reverse remodeling of the left ventricular myocardium, especially in patients with ischemic chronic heart failure, with less radiation exposure to the surgeon and the patient, and without electrode-related complications. CONCLUSION: At the preoperative stage, it is recommended to perform a synchronized single-photon emission computed tomography of the myocardium with 99mTc-methoxy-isobutyl-isonitrile at rest before implantation of the CCM device to assess the presence of scar zones/myocardial fibrosis in the anterior and inferior septal regions of the interventricular septum of the left ventricle, followed by implantation of ventricular electrodes in the zone of the minor scar/fibrous lesion, which will allow to achieve optimal stimulation parameters, increase the effectiveness of CCM therapy, reduce the radiation exposure on medical personnel and the patient during surgery.
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Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Persona de Mediana Edad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Fibrilación Atrial/cirugía , Anciano , Resultado del Tratamiento , Electrodos Implantados , Volumen Sistólico/fisiología , Tomografía Computarizada de Emisión de Fotón Único/métodos , Ecocardiografía/métodos , Contracción Miocárdica/fisiologíaRESUMEN
BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.
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BACKGROUND: There is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem cell therapy in patients with chronic heart failure (HF). METHODS: Using a systematic approach, eligible randomized controlled trials (RCTs) of stem cell therapy (BMMNCs or MSCs) in patients with HF were retrieved to perform a meta-analysis on clinical outcomes (major adverse cardiovascular events (MACE), hospitalization for HF, and mortality) and echocardiographic indices (including left ventricular ejection fraction (LVEF)) were performed using the random-effects model. A risk ratio (RR) or mean difference (MD) with corresponding 95% confidence interval (CI) were pooled based on the type of the outcome and subgroup analysis was performed to evaluate the potential differences between the types of cells. RESULTS: The analysis included a total of 36 RCTs (1549 HF patients receiving stem cells and 1252 patients in the control group). Transplantation of both types of cells in patients with HF resulted in a significant improvement in LVEF (BMMNCs: MD (95% CI) = 3.05 (1.11; 4.99) and MSCs: MD (95% CI) = 2.82 (1.19; 4.45), between-subgroup p = 0.86). Stem cell therapy did not lead to a significant change in the risk of MACE (MD (95% CI) = 0.83 (0.67; 1.06), BMMNCs: RR (95% CI) = 0.59 (0.31; 1.13) and MSCs: RR (95% CI) = 0.91 (0.70; 1.19), between-subgroup p = 0.12). There was a marginally decreased risk of all-cause death (MD (95% CI) = 0.82 (0.68; 0.99)) and rehospitalization (MD (95% CI) = 0.77 (0.61; 0.98)) with no difference among the cell types (p > 0.05). CONCLUSION: Both types of stem cells are effective in improving LVEF in patients with heart failure without any noticeable difference between the cells. Transplantation of the stem cells could not decrease the risk of major adverse cardiovascular events compared with controls. Future trials should primarily focus on the impact of stem cell transplantation on clinical outcomes of HF patients to verify or refute the findings of this study.
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Trasplante de Médula Ósea , Insuficiencia Cardíaca , Trasplante de Células Madre Mesenquimatosas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Insuficiencia Cardíaca/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Médula Ósea/métodos , Volumen Sistólico , Resultado del Tratamiento , Células Madre Mesenquimatosas/citología , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin's effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM: To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 µmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS: At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 µmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15-50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION: Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.
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BACKGROUND: The diagnosis and treatment of depression in patients with chronic heart failure (CHF) is challenging, with no ideal treatment at present. AIM: To analyze the clinical intervention effect of Xuefu Zhuyu decoction (XFZYD) on CHF complicated with depression. METHODS: The study cohort comprised 116 patients with CHF complicated with depression who received treatment from July 2020 to July 2023, of which 55 received Western medicine (control group) and 61 received XFZYD (research group). Data on clinical effectiveness, traditional Chinese medicine (TCM) syndrome score, cardiac function, negative emotions, and serum inflammatory factors, were collected for comparative analyses. RESULTS: Compared with the control group, the research group had an evidently higher total effective rate. Furthermore, there were marked reductions in TCM symptom score, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, Self-Rating Depression Scale, Hamilton Depression Scale, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 in the research group after treatment, and these were lower than the corresponding values in the control group. Left ventricular ejection fraction was increased and higher in the research group compared with the control group after treatment. CONCLUSION: Our findings conclusively proved that XFZYD was considerably superior to Western medicine for treating CHF complicated with depression because it significantly alleviated patients' symptoms, improved cardiac function, relieved negative emotions, and reduced the levels of serum inflammatory factors.
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OBJECTIVE: To predict the risk of in-hospital death in patients with chronic heart failure (CHF) complicated by lung infections using interpretable machine learning. METHODS: The clinical data of 1415 patients diagnosed with CHF complicated by lung infections were obtained from the MIMIC-IV database. According to the pathogen type, the patients were categorized into bacterial pneumonia and non-bacterial pneumonia groups, and their risks of in-hospital death were compared using Kaplan-Meier survival curves. Univariate analysis and LASSO regression were used to select the features for constructing LR, AdaBoost, XGBoost, and LightGBM models, and their performance was compared in terms of accuracy, precision, F1 value, and AUC. External validation of the models was performed using the data from eICU-CRD database. SHAP algorithm was applied for interpretive analysis of XGBoost model. RESULTS: Among the 4 constructed models, the XGBoost model showed the highest accuracy and F1 value for predicting the risk of in-hospital death in CHF patients with lung infections in the training set. In the external test set, the XGBoost model had an AUC of 0.691 (95% CI: 0.654-0.720) in bacterial pneumonia group and an AUC of 0.725 (95% CI: 0.577-0.782) in non-bacterial pneumonia group, and showed better predictive ability and stability than the other models. CONCLUSION: The overall performance of the XGBoost model is superior to the other 3 models for predicting the risk of in-hospital death in CHF patients with lung infections. The SHAP algorithm provides a clear interpretation of the model to facilitate decision-making in clinical settings.
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Insuficiencia Cardíaca , Mortalidad Hospitalaria , Aprendizaje Automático , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Masculino , Femenino , Enfermedad Crónica , Algoritmos , Neumonía/mortalidad , Neumonía/complicaciones , Neumonía Bacteriana/mortalidad , Neumonía Bacteriana/complicaciones , Anciano , Factores de Riesgo , Persona de Mediana Edad , Estimación de Kaplan-MeierRESUMEN
OBJECTIVES: To identify perceptions and experiences related to caring science and collaborative care in intervention participants of the Collaborative Care to Alleviate Symptoms and Adjust to Illness (CASA) study, a randomized, multi-site clinical trial for patients with chronic heart failure and reduced health status. METHODS: Forty-five participants completed semi-structured, telephone interviews with a focus on intervention components, impact of the intervention on participants' lives, and recommendations for intervention change. Data were analyzed using an inductive content analysis approach focusing on the presence and frequency of text to identify patterns, categories, and themes across participants without an a priori code book. The validity of the identified categories was enhanced through triangulation. RESULTS: Three themes were identified: (1) intervention providers' caring/helping attitude and caring/helping communication; (2) care team availability to respond to concerns or questions; and (3) help with understanding and navigating the healthcare system. DISCUSSION: Patients highly value caring attitudes and communication, availability, and empowerment to understand and navigate healthcare systems. These attitudes and behaviors may be important mediators of the success of collaborative care programs. These are consistent with the theory of caring science, a framework that is relevant more broadly to patient-centered and team-based care models.
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This review delves into the most recent therapeutic approaches for pediatric chronic heart failure (HF) as proposed by the International Society for Heart and Lung Transplantation (ISHLT), which are not yet publicly available. The guideline proposes an exhaustive overview of the evolving pharmacological strategies that are transforming the management of HF in the pediatric population. The ISHLT guidelines recognize the scarcity of randomized clinical trials in children, leading to a predominance of consensus-based recommendations, designated as Level C evidence. This review article aims to shed light on the significant paradigm shifts in the proposed 2024 ISHLT guidelines for pediatric HF and their clinical ramifications for pediatric cardiology practitioners. Noteworthy advancements in the updated proposed guidelines include the endorsement of angiotensin receptor-neprilysin inhibitors (ARNIs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and soluble guanylate cyclase (sGC) stimulators for treating chronic HF with reduced ejection fraction (HFrEF) in children. These cutting-edge treatments show potential for enhancing outcomes in pediatric HFrEF. Nonetheless, the challenge persists in validating the efficacy of therapies proven in adult HFrEF for the pediatric cohort. Furthermore, the proposed ISHLT guidelines address the pharmacological management of chronic HF with preserved ejection fraction (HFpEF) in children, marking a significant step forward in pediatric HF care. This review also discusses the future HF drugs in the pipeline, their mechanism of actions, potential uses, and side effects.
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BACKGROUND: Chronic heart failure (CHF) impairs cognitive function, yet its effects on brain structure and underlying mechanisms remain elusive. This study aims to explore the mechanisms behind cognitive impairment. METHODS: CHF models in rats were induced by ligation of the left anterior descending coronary artery. Cardiac function was analyzed by cardiac ultrasound and hemodynamics. ELISA, immunofluorescence, Western blot, Golgi staining and transmission electron microscopy were performed on hippocampal tissues. The alterations of intestinal flora under the morbid state were investigated via 16S rRNA sequencing. The connection between neuroinflammation and synapses is confirmed by a co-culture system of BV2 microglia and HT22 cells in vitro. Results: CHF rats exhibited deteriorated cognitive behaviors. CHF induced neuronal structural disruption, loss of Nissl bodies, and synaptic damage, exhibiting alterations in multiple parameters. CHF rats showed increased hippocampal levels of inflammatory cytokines and activated microglia and astrocytes. Furthermore, the study highlights dysregulated PDE4-dependent cAMP signaling and intestinal flora dysbiosis, closely associated with neuroinflammation, and altered synaptic proteins. In vitro, microglial neuroinflammation impaired synaptic plasticity via PDE4-dependent cAMP signaling. CONCLUSIONS: Neuroinflammation worsens CHF-related cognitive impairment through neuroplasticity disorder, tied to intestinal flora dysbiosis. PDE4 emerges as a potential therapeutic target. These findings provide insightful perspectives on the heart-gut-brain axis.
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Disfunción Cognitiva , Disbiosis , Microbioma Gastrointestinal , Insuficiencia Cardíaca , Enfermedades Neuroinflamatorias , Plasticidad Neuronal , Animales , Insuficiencia Cardíaca/microbiología , Insuficiencia Cardíaca/fisiopatología , Disfunción Cognitiva/microbiología , Disbiosis/microbiología , Ratas , Masculino , Hipocampo/metabolismo , Hipocampo/patología , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Enfermedad Crónica , Microglía/metabolismoRESUMEN
OBJECTIVE: Despite their effectiveness, cardiac rehabilitation (CR) programs have low participation and adherence rates. CR participation and adherence are directly related to the social, economic, cultural, and geographical characteristics of the society. Therefore, our study aimed to investigate the reasons behind low participation in CR within Turkish society, as well as the barriers that restrict participation despite educational efforts. METHOD: The research was conducted with participants who were over 18 years of age, had any history of heart disease, and had been hospitalized in the last year. The patients' medical history, chronic diseases, demographics, habits, employment and income status, educational status, and approaches to CR were surveyed. Additionally, patients who still did not consider participating in CR after receiving information were asked about the reasons for their decisions. RESULTS: Although 95.6% of patients were eligible for CR, 91.9% of them were previously unaware of this treatment option. After being informed, 29.4% of patients agreed to participate in CR. The most common reasons for not participating after receiving information were as follows: three days a week is too much (21.9%); this place is far away, but if it were closer, I would come (18.1%); I can't come on weekdays (15.6%); and I would come if someone brought me (14.4%). CONCLUSION: We observed that the participation rate in CR increased from 0% to 29.4% after receiving information. Furthermore, it was determined that the CR schedule and transportation were significant factors influencing participation.
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Background: Chronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR). Methods: The research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software. Results: The IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: ß = 0.015, 95% CI: 0.005-0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: ß = 0.02, 95% CI: 0.010-0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO. Conclusion: Genetic evidence indicates a positive correlation between CHF and pars opercularis TH.
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Pulmonary thromboembolism (PE) is a potential major complication in patients with chronic Chagas heart disease (CChD). The source of PE is the right-sided chambers instead of deep vein thrombosis. Little is known regarding risk factors, clinical picture, and the clinical course of patients with PE secondary to CChD. The aim of this review was to try to provide doctors with such data. We searched for papers related to PE in CChD patients in the PUBMED from 1955 to 2020. Twenty-six manuscripts were retrieved, of which 12 fulfilled entry criteria and were included in the study. Right-sided cardiac thrombosis or PE was confirmed on morphological or imaging studies. A total of 431 patients with PE were reported. Age varied from 30 to 85 years. About 332 patients were reported to have chronic heart failure (CHF), whereas 41 (9%) sudden cardiac death (SCD) at autopsy. Clinical manifestations reported were sudden onset dyspnea was found in 1 patient, haemoptysis in 2, worsening CHF in 2, and chest pain in 1. An X-ray chest was reported for 6 patients: abnormalities consistent with PE were found in 3. The resting electrocardiogram (ECG) was reported for 5 patients: it was abnormal in all. One study reported a mean left ventricular ejection fraction of 42.1 ± 18.7%. The prevalence of right-sided cardiac thrombosis varied from 66% to 85% patients. PE was the cause of death in 17% of patients. The clinical diagnosis of PE in patients with Chagas cardiomyopathy (ChCM) is very difficult in the absence of a prediction score that performs well. However, in the presence of haemoptysis or worsening heart failure (HF), abnormal ECG, or chest X-ray, the diagnosis of PE should be raised, and patients promptly referred to detailed Doppler Tissue Echocardiography and computed tomography angiography, and treated in a timely manner.
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Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). KaplanâMeier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. KaplanâMeier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.
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Background: The pathogenesis and development of chronic heart failure (CHF) may involve long non-coding ribonucleic acid (lncRNA) steroid receptor RNA activator 1 (SRA1), a known cardiomyopathy risk factor and regulator of cardiac myofibroblast activation. This study aimed to investigate the application of SRA1 in the early detection and prediction of CHF. Methods: SRA1 plasma expression was determined in CHF patients and healthy individuals/using real time-quantitative polymerase chain reaction (RT-qPCR). The diagnostic and prognostic value of SRA1 was assessed using receiver operating curve (ROC) and Cox regression analyses. Results: Compared with the healthy controls, the patients with CHF had increased brain natriuretic peptide (BNP) levels, left atrial end-systolic diameter (LAD), left ventricular end-diastolic diameter (LVDd), and decreased left ventricular ejection fraction (LVEF). SRA1 was significantly upregulated in CHF patients as well as positively correlated with BNP level, LAD, and LVDd, and negatively correlated with LVEF. SRA1 could sensitively discriminate CHF patients from healthy individuals and was an independent predictor of adverse event-free survival in CHF patients. Conclusions: Upregulated plasma SRA1 can discriminate patients with CHF from healthy individuals and predict adverse outcomes in CHF patients. Thus, SRA1 is a potential molecular indicator for monitoring chronic heart failure development.
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INTRODUCTION AND OBJECTIVES: Spot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF. METHODS: This observational and ambispective study included 1145 outpatients with chronic HF followed in a single center specialized HF clinic. UNa+ assessment was carried out 1-5 days before each visit. The endpoints of the study were the association between UNa+ and risk of a) long-term death and b) AHF-hospitalization and total WHF events (including AHF-hospitalization, emergency department visits or parenteral loop-diuretic administration in HF clinic), assessed by multivariate Cox and negative binomial regressions. RESULTS: The mean±standard deviation of age was 73±11 years, 670 (58.5%) were men, 902 (78.8%) were on stable NYHA class II, and 595 (52%) had LFEF ≥50%. The median (interquartile range) UNa+ was 72 (51-94) mmol/L. Over a median follow-up of 2.63 (1.70-3.36) years, there were 293 (25.6%) deaths and 382 WHF events (244 AHF-admissions) in 233 (20.3%) patients. After multivariate adjustment, baseline UNa+ was inverse and linearly associated with the risk of total WHF (IRR, 1.07; 95%CI, 1.02-1.12; P=.007) and AHF-admissions (IRR, 1.08; 95%CI, 1.02-1.14; P=.012) and borderline associated with all-cause mortality (HR, 1.04; 95%CI, 0.99-1.09; P=.068). CONCLUSIONS: In outpatients with chronic HF, lower UNa+ was associated with a higher risk of recurrent WHF events.
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This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.