Treatment Of Heart Failure Research Articles

Exploring the Potential Effects and Mechanism of Astragalus Membranaceus in Treating Ischemic Heart Failure Based on Network Pharmacology and Experimental Verification.

Astragalus membranaceus (AM) is a traditional Chinese medicine that has been clinically utilized as an adjunctive therapy for the treatment of myocardial ischemia and heart failure; however, its precise molecular mechanism of action remains unknown. This study aims to investigate the potential pharmacological effects and molecular mechanism of AM in the treatment of ischemic heart failure (IHF) using network pharmacology methods, molecular docking technology, and in vitro experiments. The active components and targets of AM were obtained from the TCMSP databases, while the disease targets of IHF were retrieved from GeneCards and OMIM databases. The analysis of overlapping targets between AM and IHF mainly included active compounds-targets network, PPI network, and GO and KEGG enrichment analysis. The association between active compounds and target proteins was verified through molecular docking. Additionally, an in vitro experimental model was used to evaluate the accuracy of the forecast results. The network pharmacological analysis revealed that quercetin, kaempferol, 7-Omethylisomucronulatol, formononetin, and isorhamnetin were the core active components of AM in treating IHF. The core targets included AKT1, IL6, IL1B, PTGS2, CASP3, MMP9, and HIF1A. The molecular docking results demonstrated a strong binding affinity between these active components and targets. The KEGG pathway analysis suggested that the PI3K-AKT signaling pathway might play a central role in mediating AM's therapeutic effects on IHF. In vitro experiments demonstrated that AM treatment enhanced cell viability, reduced heart failure biomarkers, and suppressed cell apoptosis. Furthermore, the western blot analyses indicated that AM treatment effectively regulated AKT1 phosphorylation in an experimental model of IHF. Through integrated network pharmacological analysis, molecular docking technology, and in vitro experimental validation, it was demonstrated that AM can effectively mitigate IHF through activating PI3K-AKT signaling pathway. These findings significantly advance our understanding of the molecular mechanisms in IHF treatment and contribute further to promoting the clinical application of AM.

Exploring the Experience of Guo Yi Master Lei Zhongyi in Dialectical Treatment of Heart Failure Based on the Theory of "Yang Wei Yin Xian"

The term "heart failure" first appeared in Wang Shuhe's "Meridian: Spleen and Stomach Diseases". The related description of heart failure is recorded in the "Huangdi Neijing", which is a disease mainly characterized by palpitations, asthma, and edema. It is often the terminal stage of chronic heart disease that cannot be cured. Its basic pathogenesis is prolonged illness with deficiency of heart qi, loss of nourishment in the heart, weakness in blood circulation, prolonged stagnation of the heart meridians, cessation of water consumption, and the generation of phlegm and dampness, resulting in heart failure. The theory of "Yang Wei Yin Xian" is a highly summarized understanding by Zhang Zhongjing of the etiology and pathogenesis of chest pain and heartache. Chinese medical master Lei Zhongyi has been practicing medicine for more than 60 years and has unique insights in the prevention and treatment of heart failure, with considerable clinical efficacy. He believes that heart failure belongs to the principle of deficiency and excess, and the theory of "yang micro yin string" is also applicable to this disease. Its onset is closely related to the pathological changes of substances such as qi, blood, and body fluids. The method of treating phlegm and blood stasis together should run through the treatment process, especially for patients who consume qi and yin in the later stage. Emphasis should be placed on promoting blood circulation and nourishing qi and yin, and the treatment should focus on both attacking and tonifying, with Qi and blood regulating simultaneously. Based on clinical experience, the original Yangxin Huoxue Tang has achieved significant clinical efficacy.

Empagliflozin attenuates hypoxia-induced heart failure of zebrafish embryos via influencing MMP13 expression

BackgroundToday, sodium glucose co-transporter 2 (SGLT2) inhibitors are more than diabetes drugs. They are also indicated in chronic heart failure (HF) treatment in both diabetic and non-diabetic patients, independently of the ejection fraction. Multiple mechanisms have been suggested behind the cardioprotective effects of SGLT2 inhibitors. However, the underlying mechanisms still remain largely unexplored. Here, we used a zebrafish embryo model to search for new potential players whereby SGLT2 inhibitors attenuate HF. MethodsHF in zebrafish embryos was caused exposing them to chemically induced hypoxia. As a SGLT2 inhibitor, we used empagliflozin. Its effect on hypoxia-induced HF of the embryos was evaluated using video microscopy and calculation of fractional shortening (FS) of embryos´ hearts. RT-qPCR of brain natriuretic peptide (bnp) expression was also used to examine empagliflozin´s effect on HF. Transcriptome analysis of total RNA of the embryos was performed to search for new potential mechanisms contributing to the beneficial effect of empagliflozin on HF. ResultsEmpagliflozin significantly attenuated hypoxia-induced HF of zebrafish embryos as shown with improved FS of the hearts and decreased bnp expression. Transcriptome analysis revealed that the improvement of HF in response to empagliflozin was accompanied with decreased matrix metalloproteinase 13a (mmp13a) expression. Treatment of hypoxia-induced embryos with MMP13 inhibitor ameliorated the impaired heart function accordingly to the effect of empagliflozin. MMP13 inhibitor was not toxic to the embryos. ConclusionsOur study shows that empagliflozin´s favorable effect on attenuating HF is mediated via MMP13. MMP13 provides a novel option when developing new therapeutics for HF treatment.

Effect of an Enteral Formula Enriched with ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model.

Malnutrition is known to worsen the prognosis of chronic heart failure. To gain information that may be helpful in establishing appropriate nutritional interventions for chronic heart failure, the present study was performed to investigate the efficacy of nutritional management with two enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat heart failure model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. Additionally, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a heart failure model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic heart failure.

Sodium-Glucose Cotransporter-2 Inhibitors In Heart Failure

Heart failure (HF) is a serious problem in a modern world, with increasing prevalence among ageing populations. The use of sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally intended to treat type 2 diabetes, has revolutionised the treatment of HF. In this review article, we present the latest evidence on the mechanism of action of SGLT2 inhibitors, also called flosins, in HF. The primary mechanism of action of flosins is to reduce glucose reabsorption from glomerular filtration in the proximal renal tubule with a concomitant reduction in sodium reabsorption, leading to urinary glucose excretion and osmotic diuresis. Based on experimental findings, several pleiotropic effects of SGLT2 inhibitors have been proposed. Mechanisms also include regulation of inflammatory and oxidative pathways along with improved endothelial function. Recent multicentre studies of SGLT2 inhibitors have shown that they reduce hospitalisations for heart failure after their use, regardless of type 2 diabetes and the degree of cardiac systolic dysfunction.

Beta-Blocker in Heart Rate Control and Cardio Protection: The Role of ADRB1 Variants and HCN4 Regulation – A Systematic Review

Elevated heart rate is linked to adverse cardiovascular outcomes. Sinoatrial (SA) nodes, hyperpolarization-activated cyclic nucleotide-gated-4 (HCN4) channels, and beta1-adrenergic receptor (ADRB1) are responsible for generating the heart rate. Beta-blockers have a cardioprotective effect on heart failure, including controlling heart rate. However, the responses to beta-blockers can vary among individuals. ADRB1 genetic variability may be contributed to the differential beta-blocker effect in heart failure. HCN4 also performs a crucial function in the pacemaker cells of the heart. Exploring the effect of beta-blockers in pacemaker cells is expanding the view of their role and their therapeutic response in heart failure. The objectives of this study were to identify ADRB1 genetic variants affecting heart rate response in heart failure subjects with beta-blocker treatment and to explore the effect of beta-blockers on HCN4 channels and SA nodes. A systematic review was performed using three databases. Eight of 668 manuscripts were selected. The systematic review found that ADRB1 genetic variants (A145G (Ser49Gly) and C1165G (Arg389Gly)) can affect heart rate response in beta-blocker-treated heart failure. The study also found that the percentage of patients with the Ser49Ser-Gly389X haplotype achieved a heart rate target was higher than other haplotypes. Individuals with the Arg389Arg genotype necessitated a markedly increased amount of beta-blocker dose to reach the identical heart rate target compared to those with the Gly389X gene variation. In addition, the review found that carvedilol, a beta-blocker derivative, demonstrated beneficial effects in inhibiting HCN-gated channels. Bisoprolol and carvedilol improved channel regulation in the SA Node by reversing the downregulation of HCN4 and sodium channels. In general, this systematic review provides important insights into beta-blockers in treating heart failure, specifically concerning the genetic variability of ADRB1 and the beta-blockers effect on the SA node and HCN4 channels.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Iron Deficiency and its Relationship with Chronic Heart Failure- A Review.

This review article discusses multifactorial pathophysiology, the relationship between clinical characteristics, functional and absolute ID, and the advantages of medicinal intervention in chronic heart failure (CHF). It also covers how iron shortage affects other body parts. The most recent publications that included substantial scientific data on the connection between CHF and ID, with or without anaemia, were selected. Complex physiopathological interactions, including higher hepcidin levels, systemic inflammation, and activation of the renin-angiotensin-aldosterone system, have been identified in these patients. These mechanisms exacerbate the outcomes for patients by amplifying the severity of anemia, chronic heart failure (CHF), and Chronic kidney disease (CKD). Research in this area has been limited and has shown inconsistent findings. Still, it has also examined evidence-based treatment approaches and diagnostic guidelines, especially in relation to iron supplements and erythropoietin-stimulating medications. Anemia is a frequent chronic heart failure consequence and a poor prognostic factor. We still don't completely understand the many complex causes of anemia. Iron deficiency screening is highly recommended for people with cardiac ailments because of its significance for their prognoses. Due to the paucity of research proving its effectiveness, the high incidence of unfavourable gastrointestinal side effects, and the prolonged length of time required for treatment to boost haemoglobin levels, an oral iron supplement is not advised for people with chronic heart failure. An insufficient amount of iron not only impacts the heart but also various other body components.

Socio-economic inequalities and heart failure morbidity and mortality: A systematic review and data synthesis.

Socio-economic status (SES) has been associated with incident and prevalent heart failure (HF), as well as its morbidity and mortality. However, the precise nature of the relationship between SES and HF remains unclear due to inconsistent data. This study aims to provide a comprehensive assessment and data synthesis of the relationship between SES and HF morbidity and mortality. We performed a systematic search and data synthesis using six databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The included studies comprised observational studies that reported on HF incidence and prevalence, HF hospitalizations, worsening HF (WHF) and all-cause mortality, as well as treatment options (medical, device and advanced HF therapies). SES was measured on both individual and area levels, encompassing single (e.g., income, education, employment, social risk score, living conditions and housing characteristics) and composite indicators. Among the 4124 studies screened, 79 were included, with an additional 5 identified through cross-referencing. In the majority of studies, a low SES was associated with an increased HF incidence (72%) and prevalence (75%). For mortality, we demonstrated that low SES was associated with increased mortality in 45% of the studies, with 18% of the studies showing mixed results (depending on the indicator, gender or follow-up) and 38% showing non-significant results. Similar patterns were observed for the association between SES, WHF, medical therapy prescriptions and the utilization of devices and advanced HF therapies. There was no clear pattern in the used SES indicators and HF outcomes. This systematic review, using contemporary data, shows that while socio-economic disparity may influence HF incidence, management and subsequent adverse events, these associations are not uniformly predictive. Our review highlights that the impact of SES varies depending on the specific indicators used, reflecting the complexity of its influence on health disparities. Assessment and recognition of SES as an important risk factor can assist clinicians in early detection and customizing HF treatment, while also aiding policymakers in optimizing resource allocation.

Bridging the Gap: Advances and Challenges in Heart Regeneration from In Vitro to In Vivo Applications.

Cardiovascular diseases, particularly ischemic heart disease, area leading cause of morbidity and mortality worldwide. Myocardial infarction (MI) results in extensive cardiomyocyte loss, inflammation, extracellular matrix (ECM) degradation, fibrosis, and ultimately, adverse ventricular remodeling associated with impaired heart function. While heart transplantation is the only definitive treatment for end-stage heart failure, donor organ scarcity necessitates the development of alternative therapies. In such cases, methods to promote endogenous tissue regeneration by stimulating growth factor secretion and vascular formation alone are insufficient. Techniques for the creation and transplantation of viable tissues are therefore highly sought after. Approaches to cardiac regeneration range from stem cell injections to epicardial patches and interposition grafts. While numerous preclinical trials have demonstrated the positive effects of tissue transplantation on vasculogenesis and functional recovery, long-term graft survival in large animal models is rare. Adequate vascularization is essential for the survival of transplanted tissues, yet pre-formed microvasculature often fails to achieve sufficient engraftment. Recent studies report success in enhancing cell survival rates in vitro via tissue perfusion. However, the transition of these techniques to in vivo models remains challenging, especially in large animals. This review aims to highlight the evolution of cardiac patch and stem cell therapies for the treatment of cardiovascular disease, identify discrepancies between in vitro and in vivo studies, and discuss critical factors for establishing effective myocardial tissue regeneration in vivo.

Heart Failure Care Facilitators and Barriers in Rural Haiti: A Qualitative Study

Background: Heart failure (HF) is a leading cause of hospitalizations in Haiti. However, few patients return for outpatient care. The factors contributing to chronic HF care access are poorly understood. Objective: The purpose of this study is to investigate the facilitators and barriers to accessing care for chronic HF from the patients’ perspectives. Methods: We conducted a qualitative descriptive study of 13 patients with HF participating in three group interviews and one individual interview. We recruited patients after discharge from a nongovernmental organization-supported academic hospital in rural Haiti. We employed thematic analysis using emergent coding and categorized themes using the socioecological model. Findings: Facilitators of chronic care included participants’ knowledge about the importance of treatment for HF and engagement with health systems to manage symptoms. Social support networks helped participants access clinics. Participants reported low cost of care at this subsidized hospital, good medication accessibility, and trust in the healthcare system. Participants expressedstrong spiritual beliefs, with the view that the healthcare system is an extension of God’s influence. Barriers to chronic care included misconceptions about the importance of adherence to medications when symptoms improve and remembering follow-up appointments. Unexpectedly, participants believed they should take their HF medications with food and that food insecurity resulted in missed doses. Lack of social support networks limited clinic access. The nonhealthcare costs associated with clinic visits were prohibitive for many participants. Participants expressed low satisfaction regarding the clinic experience. A barrier to healthcare was the belief that heart disease caused by mystical and supernatural spirits is incurable. Conclusions: We identified several facilitators and barriers to chronic HF care with meaningful implications for HF management in rural Haiti. Future interventions to improve chronic HF care should emphasize addressing misconceptions about HF management and fostering patient support systems for visit and medication adherence. Leveraging local spiritual beliefs may also promote care engagement.

Optimizing heart failure therapy with enhanced medical management: focus on heart rate management

Heart failure (HF) is a significant global health issue, affecting over 60 million people worldwide, with its prevalence expected to rise due to aging populations and the increasing incidence of comorbidities like hypertension and diabetes. Despite therapeutic advances, including quadruple therapy with renin-angiotensin-system inhibitors, beta blockers (BB), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors, HF remains a condition with a poor prognosis, particularly for those with reduced ejection fraction (HFrEF), who are predominantly found in low- and middle-income countries like India. Elevated resting heart rate (HR) is a critical prognostic factor in HF, correlating strongly with cardiovascular mortality and morbidity. For every five-beat increase in HR, there is a 16% rise in cardiovascular mortality and HF hospitalization, emphasizing the need for effective HR management. However, challenges persist in optimizing HF treatment, such as the underutilization of BBs, despite their proven efficacy in reducing mortality. In India, the "double burden" of age-related and contemporary diseases complicates HF management further. Addressing unmet needs in HF care requires optimizing therapeutic strategies and improving treatment adherence, particularly in the context of HR control. Studies indicate that tailored approaches, including the use of BBs and ivabradine, could reduce HR and improve clinical outcomes. The ongoing challenges in accessing guideline-directed therapy and ensuring adherence highlight the need for comprehensive strategies to enhance patient outcomes, while personalized treatments and further research remain essential in navigating the complex landscape of HF management.

Évaluation préliminaire de l'intérêt d'une cellule d'optimisation thérapeutique sur la titration des traitements de l'insuffisance cardiaque à fraction d’éjection ventriculaire gauche réduite et la qualité de vie des patients

IntroductionA multidisciplinary therapeutic optimization unit (COT) was created in January 2023 at Versailles Hospital, aimed at therapeutic optimisation of patients with chronic heart failure with reduced left ventricular ejection fraction. The objective of the study was to assess the impact of the first year of COT activity on the sequential implementation and titration of heart failure treatments, the clinical evolution, and improvement of patients’ quality of life. MethodsThis prospective study included consecutive patients treated by the COT after hospitalisation for acute heart failure, from January to December 2023. Clinical, biological, titration, and tolerance data were analysed. Quality of life was assessed at baseline and at the end of the follow-up by COT, using standardized SF-12 and EQ-5D questionnaires. ResultsWe included 90 patients (men 73%, mean age 67 years). The mean left ventricular ejection fraction was 34 ± 10 %. At final visit (median number of visits 4 ; median follow-up duration 156 days), 76.7% of patients achieved optimisation with respect to maximum individually tolerated doses, but only 13.3% with respect to theoretical maximum doses for the four therapeutic classes. At 1-year follow up, total mortality was 4.4% (4/90), and 9 patients (10%) were rehospitalised unplanned for acute heart failure. COT monitoring was associated with significant improvement in NYHA class, left ventricular ejection fraction, and SF-12 and EQ-5D-5L quality of life scores. ConclusionAlthough titration of heart failure treatments remained suboptimal, significant improvement was observed for NYHA class, left ventricular ejection fraction, and patient quality of life parameters.

Concentric remodeling and the metabolic-associated steatotic liver disease in patients with type 1 diabetes: an exploratory study.

Diabetic cardiomyopathy in young patients with type 1 diabetes (T1D) usually presents as asymptomatic diastolic heart dysfunction with left ventricle (LV) remodeling. Its prevalence seems to be underestimated. One of the factors seemingly influencing LV remodeling is a metabolic-associated steatotic liver disease (MASLD), which was extensively investigated in patients with type 2 diabetes but not with T1D. This study aimed to describe the correlation between MASLD risk and relative wall thickness (RWT) in young patients with T1D without heart failure symptoms or treatment. Study participants were recruited at the inpatient diabetology department, in admission order. Patients underwent a set of laboratory tests and echocardiographic examinations. The risk of MASLD was estimated using fatty liver index (FLI). Acquired data was then statistically analyzed. The study group consisted of 55 patients. 25 participants had RWT > 0.42, suggesting LV remodeling. Study participants did not differ in HbA1c, NT-proBNP, HDL, LDL, non-HDL, and uric acid concentrations. However, patients with RWT > 0.42 had higher FLI (40.97 vs. 13.82, p < 0.01) and BMI (27.3 vs. 22.5, p < 0.01) and differed in transaminase concentrations. Moreover, patients with RWT > 0.42 had significantly higher LV mass index (85.6 vs. 68.2g/m2) and altered mitral ring velocities. In univariable logistic regression, FLI correlated with LV remodeling risk (OR 1.028, p = 0.05). The optimal cutoff point for FLI predicting the RWT > 0.42 was 26.38 (OR 10.6, p = 0.04, sensitivity 0.857, specificity 0.657). FLI correlates with RWT in patients with T1D independently of diabetes metabolic control and hypothetically may support recognizing T1D patients with a higher risk of LV remodeling.

Changes in urinary output due to concomitant administration of sacubitril/valsartan and atrial natriuretic peptide in patients with heart failure: a multicenter retrospective cohort study

BackgroundSacubitril/valsartan is an angiotensin receptor neprilysin inhibitor (ARNI) that inhibits the degradation of endogenous natriuretic peptides. Therefore, ARNIs may increase the efficacy of human atrial natriuretic peptide (hANP), a drug for acute heart failure, by mediating its pharmacological mechanism. This study was aimed at evaluating the effects of ARNIs on the pharmacological effects of hANP by using surrogate marker, such as urinary output, in patients with heart failure.MethodsIn this multicenter retrospective cohort study, adult patients with heart failure who were taking angiotensin II receptor blockers (ARB) or ARNIs combined with hANP were enrolled. Information on basic characteristics, clinical laboratory data, medical history, and severity of cardiac insufficiency were collected from electronic medical records. The primary outcome was the change in adjusted fluid balance, calculated by IN-volume (mL/day) – OUT-volume (mL/day) / daily hANP dosage (μg).ResultsNinety-two and 62 patients in the ARB + hANP and ARNI + hANP groups, respectively, were eligible for analysis. The adjusted fluid balance in the ARNI + hANP group was significantly lower than that in the ARB + hANP group (p = 0.001). After propensity score matching, 27 patients from each group were included. Similarly, there was a significant reduction in adjusted fluid balance in the ARNI + hANP group after propensity score matching (p = 0.026).ConclusionsThese findings suggest that ARNIs may enhance the efficacy of hANP and the combination of the two may be effective in the treatment of heart failure.

A novel electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH for rapid detecting warning markers-BNP of heart failure caused by myocardial infarction

Heart failure (HF) is an insidious and dangerous disease that significantly impairs a patient’s quality of life and safety. It is not easy to detect in mild cases, and once it progresses to severe stages, deterioration can be rapid and challenging to reverse. Currently, early warning and prognostic risk assessment technologies are lacking, and there is an urgent need for precise early warning, risk assessment and diagnosis and treatment of HF at the cellular or molecular level. In this study, an electrochemical immunosensor based on AuNPs/PNR/CS@MWCNTs-COOH was prepared to detect brain natriuretic peptide (BNP), a biomarker for early warning of HF caused by myocardial infarction. Among them, the CS@MWCNTs-COOH nanocomposites and the polymerized neutral red (PNR) films on the electrode surface effectively enhanced the conductivity of the modified electrodes and significantly increased the specific surface area through the formation of three-dimensional nanostructures. AuNPs loaded on PNR/CS@MWCNTs-COOH provided a stable gold-ammonia bond for the specific antibody loading of BNP, facilitating the development of an electrochemical immunosensor with high selectivity for BNP detection. Furthermore, this work used cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) to improve aspects that influence the immunosensor’s analytical performance. Under ideal conditions, the immunosensor was tested for immunological qualities using differential pulse voltammetry (DPV), resulting in sensitive measurement of BNP concentration in undiluted serum samples.The peak current Ip of the response signal is linearly proportional to the LgCBNP in the range of 1.95 × 10−3 ng mL−1 to 8.0 ng mL−1, with a detection limit of 0.80 × 10−3 ng mL−1 (S/N=3). It can achieve highly sensitive identification and detection of trace BNP in complex biological samples and provide a convenient and efficient method for HF-related marker detection. Furthermore, it also can serve as a scientific basis and a new method for the development of early warning technology for HF and related pathological mechanism research.

Electroactive Nanomaterials for the Prevention and Treatment of Heart Failure: From Materials and Mechanisms to Applications.

Heart failure (HF) represents a cardiovascular disease that significantly threatens global well-being and quality of life. Electroactive nanomaterials, characterized by their distinctive physical and chemical properties, emerge as promising candidates for HF prevention and management. This review comprehensively examines electroactive nanomaterials and their applications in HF intervention. It presents the definition, classification, and intrinsic characteristics of conductive, piezoelectric, and triboelectric nanomaterials, emphasizing their mechanical robustness, electrical conductivity, and piezoelectric coefficients. The review elucidates their applications and mechanisms: 1) early detection and diagnosis, employing nanomaterial-based sensors for real-time cardiac health monitoring; 2) cardiac tissue repair and regeneration, providing mechanical, chemical, and electrical stimuli for tissue restoration; 3) localized administration of bioactive biomolecules, genes, or pharmacotherapeutic agents, using nanomaterials as advanced drug delivery systems; and 4) electrical stimulation therapies, leveraging their properties for innovative pacemaker and neurostimulation technologies. Challenges in clinical translation, such as biocompatibility, stability, and scalability, are discussed, along with future prospects and potential innovations, including multifunctional and stimuli-responsive nanomaterials for precise HF therapies. This review encapsulates current research and future directions concerning the use of electroactive nanomaterials in HF prevention and management, highlighting their potential to innovating in cardiovascular medicine.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Induced pluripotent stem cell therapies in heart failure treatment: ameta-analysis and systematic review.

Background: Heart failure (HF) causes over 266,400 deaths annually. Despite treatment advancements, HF mortality remains high. Induced pluripotent stem cells (iPSCs) offer promising new options. This review assesses iPSC-based treatments for HF.Method: the review included studies from PubMed, ScienceDirect and Web of Science.Results: Analysis of 25 studies with 553 animals showed a baseline ejection fraction (EF) of 39.2±8.9%. iPSC treatment significantly improved EF (MD=8.6, p<0.001) and fractional shortening (MD=6.38, p<0.001), and reduced ventricular remodeling without increasing arrhythmia risk.Conclusion: iPSC-based therapy improves heart function and reduces ventricular volumes in HF animal models, aligning with promising early clinical trial outcomes.

Implications of β-Arrestin biased signaling by angiotensin II type 1 receptor for cardiovascular drug discovery and therapeutics

Angiotensin II receptors, Type 1 (AT1R) and Type 2 (AT2R) are 7TM receptors that play critical roles in both the physiological and pathophysiological regulation of the cardiovascular system. While AT1R blockers (ARBs) have proven beneficial in managing cardiac, vascular and renal maladies they cannot completely halt and reverse the progression of pathologies. Numerous experimental and animal studies have demonstrated that β-arrestin biased AT1R-ligands (such as SII-AngII, S1I8, TRV023, and TRV027) offer cardiovascular benefits by blocking the G protein signaling while retaining the β-arrestin signaling. However, these ligands failed to show improvement in heart-failure outcome over the placebo in a phase IIb clinical trial. One major limitation of current β-arrestin biased AT1R-ligands is that they are peptides with short half-lives, limiting their long-term efficacy in patients. Additionally, β-arrestin biased AT1R-ligand peptides, may inadvertently block AT2R, a promiscuous receptor, potentially negating its beneficial effects in post-myocardial infarction (MI) patients. Therefore, developing a small molecule β-arrestin biased AT1R-ligand with a longer half-life and specificity to AT1R could be more effective in treating heart failure. This approach has the potential to revolutionize the treatment of cardiovascular diseases by offering more sustained and targeted therapeutic effects.