HF Treatment Research Articles

Effects of Different Fertilization Treatments on Bacterial Community and Citrus Quality in Yellow Soils of the Yunnan-Guizhou Plateau

To investigate the intrinsic driving mechanism of citrus yield and quality enhancement under different fertilizer applications, a field experiment was conducted to study the effects of biochar （SW）, organic fertilizer （YJ）, farmyard manure （NJ）, chemical fertilizer （HF）, and no fertilizer as the control （CK） on soil physical and chemical properties, bacterial community characteristics, and citrus quality of citrus orchards in the yellow soil area of the Yunnan-Guizhou Plateau. The results showed that compared with those in the CK treatment, the yield, single fruit weight, edible rate, juice rate, vitamin C content, and soluble solids of citrus increased under the different fertilization treatments. In contrast, the titratable acid content of citrus decreased, resulting in an increase in the solid-acid ratio of citrus. Among the different fertilization treatments, the most significant effective treatment was SW. The SW and YJ treatments significantly increased the soil pH value, while the HF treatment decreased soil pH. Different fertilization treatments could increase the contents of soil organic matter, hydrolyzable nitrogen, available phosphorus, and available potassium. The SW treatment exhibited the most obvious effect on the contents of soil hydrolyzable nitrogen, available phosphorus, and available potassium. The YJ treatment exhibited the most obvious effect on the soil organic matter content. The different fertilization treatments significantly affected soil bacterial community diversity and community structure, among which the SW treatment significantly increased the soil Chao1 index, observed species index, and Shannon index； optimized soil bacterial community structure； and made the bacterial symbiotic network simple and stable. By contrast, the HF treatment significantly decreased the soil Chao1 index, observed species index, and Simpson index and had less effect on bacterial community structure. Redundancy analysis showed that soil available potassium （96.47%）, Chao1 index （73.80%）, and Chujaibacter （55.92%） were the key factors in improving citrus yield and quality. Variance decomposition analysis indicated that the soil bacterial community structure was the largest contributor （17.00%） to the improvement in citrus yield and quality. In conclusion, fertilization can effectively improve soil physical and chemical properties, increase soil nutrient supply level, optimize bacterial community structure, and improve citrus yield and quality. Of these, biochar can be used as a priority for the fertilization and improvement of the soil in citrus orchards in the yellow soil area of the Yunnan-Guizhou Plateau.

Mechanism of jianxin granules in the treatment of heart failure based on proteomics and metabolomics

BackgroundHeart failure (HF) is associated with high mortality and rehospitalization rates, highlighting the need for novel therapeutic approaches. Jianxin (JX) granules, a Traditional Chinese Medicine formulation, have been patented for the treatment of HF. However, the specific therapeutic effects and underlying mechanisms of JX granules have not been fully elucidated. This study aimed at investigating the effects and mechanism of JX granules in the treatment of HF based on proteomics and metabolomic profiling.MethodsHF model was established in rats by ligation of left coronary artery. The successfully modeled rats were randomly divided into three groups: the model group, the JX granules group, and Sacubitril/Valsartan (S/V) group. Four weeks after treatment, left ventricular (LV) function was evaluated via echocardiography. LV fibrosis and apoptosis were examined through histological analyses, while mitochondrial morphology was assessed using transmission electron microscopy. Quantitative assessment of oxidative stress was also conducted. Proteomics was used to identify the differentially expressed proteins and potential pathways. Metabolomics was utilized to elucidate the variations in metabolism. Then western blotting and in vitro analyses were performed.ResultsA rat model of HF was established, evidenced by a decrease in left ventricular ejection fraction (LVEF), stroke volume (SV), and left ventricular fractional shortening (LVFS), alongside diminished adenosine triphosphate (ATP) content, elevated oxidative stress, augmented apoptosis, and disrupted pyruvate metabolism. Treatment with JX granules ameliorated these effects, improving systolic function, reducing ventricular chamber size, and increasing LVEF, SV, and LVFS, as assessed by echocardiography. Additionally, JX granules attenuated cardiac fibrosis and improved mitochondrial structure, as evidenced by less vacuolation and clearer mitochondrial cristae, when compared to the model group. The treatment also regulated apoptosis-related protein expression, partially reversing the increase in cleaved Caspase-9, cleaved Caspase-3, and Bax and the suppression of Bcl-2 observed in the heart failure rats. All of these effects were similar to S/V. Proteomic and metabolomic analyses identified key differential genes, such as triosephosphate isomerase 1 (TPI1), lactate dehydrogenase B (LDHB), pyruvate kinase M (PKM), protein kinase B (Akt), Pyruvate Dehydrogenase Beta (PDHB) and lactate dehydrogenase A (LDHA), as well as vital pathways including carbon metabolism, the PI3K-Akt signaling pathway, pyruvate metabolism, and HIF-1α signaling pathway. Moreover, JX granules mitigated oxidative stress, inhibited apoptosis, and activated Akt in H9c2 cells exposed to angiotensin II, which could be reversed by the PI3K inhibitor LY294002.ConclusionJX granules improve HF in parallel to the efficacy of S/V, at least in part, through enhancing pyruvate metabolism, inhibiting oxidative stress and activating PI3K/Akt pathway.

A Facile Microwave-Promoted Formation of Highly Photoresponsive Au-Decorated TiO2 Nanorods for the Enhanced Photo-Degradation of Methylene Blue.

The integration of noble metal nanoparticles (NPs) effectively modifies the electronic properties of semiconductor photocatalysts, leading to improved charge separation and enhanced photocatalytic performance. TiO2 nanorods decorated with Au NPs were successfully synthesized using a cost-effective, rapid microwave-assisted method in H2O2 and HF media for methylene blue (MB) degradation under visible light illumination. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 physisorption, and UV-vis spectroscopy were employed to characterize the structures, morphologies, compositions, and photoelectronic properties of the as-synthesized materials. The fusing of Au NPs effectively alters the electronic structure of TiO2, enhancing the charge separation efficiency and improved electrical conductivity. The HF treatment promotes the exposure of the highly reactive (001) and (101) crystalline facets. The improved photocatalytic activity of Au/TiO2, achieving 97% efficiency, is attributed to the surface plasmon resonance (SPR) effect of the Au NPs and the presence of oxygen vacancies. The photodegradation of MB using the TiO2/Au photocatalysts follows pseudo-first-order kinetics, highlighting the enhanced catalytic efficiency of the synthesized nanostructures. The exceptional properties of the binary Au/TiO2 photocatalysts, including the SPR effect, exposed crystallographic faces, and efficient charge carrier separation through a decrease in the recombination of electrons and holes, contribute to the photocatalytic degradation of MB.

Incidence of 1-year mortality, heart failure admissions and decompensation in patients with heart failure followed in HF units in Spain. Differences according to type of units

Abstract Introduction Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. The introduction of specific multidisciplinary HF units has improved the management of patients with this disease, thanks to better organization and management of available diagnostic and therapeutic resources. The HF Association of the ESC and the Spanish Society of Cardiology have defined 3 types of HF units (community, specialized, and advanced) according to their structure, complexity, and portfolio of services. Purpose To analyze in a contemporary registry of patients with HF followed up in HF units in Spain whether the results in terms of mortality and HF decompensations during follow-up are similar or different between the 3 types of units. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1,716 patients with HF included between 2019 and 2021 by 45 SEC-accredited HF units. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. Units were defined as community, specialized, and advanced according to ESC HFA and SEC criteria. We compared the incidence of death, HF admissions and total decompensations at 1-year follow-up between community and specialized/advanced units. Results Of the 1716 patients, 55.5% were treated in community units, 65.9% in advanced units, and 20.9% in advanced HF units. Figure 1 shows the main characteristics and treatment used in the 3 types of units. The community units treated older patients and more HFpEF, and the use of NRA and AID was lower, with no differences in the remaining characteristics, comorbidities, or treatments (Figure 1). Figure 2 shows the incidence of events at 1 year. Total mortality was 27.5% in community and 15.5% in specialized/advanced (p<0.001). HF admissions (39.7 vs 29.2%; p=0.019), HF decompensations without admission (16.4 vs 11.3%; p=0.074), total decompensations (56.1 vs 40.5%; p=0.003), and combined HF death/admissions (45.2 vs 31.4%; p=0.005) were statistically higher in community units. Control in specialized/advanced units was an independent protector factor for all events (mortality: HR 0.59, 0.43-0.82; p=0.002; HF admissions: HR 0.61, 0.42-0.90; p=0.012; total HF decompensations: HR 0.58, 0.42-0.81; p=0.001). Conclusions One-year prognosis of HF patients continues to be poor, with high rates of mortality and decompensations. Patients attended in community HF units was significantly worse in our country during the study period. Although this may be due in part to the small differences between the characteristics of the patients followed in the different types of units, it seems necessary to improve the network organization of HF care with the aim of achieving greater equity in the treatment of HF in Spain.

Effect of catheter ablation in atrial fibrillation patients irrespective of their baseline heart failure: An updated meta-analysis

Abstract Introduction Patients with atrial fibrillation (AF) are associated with higher morbidity and mortality. Catheter ablation (CA) is supposed to improve outcomes in these patients. We aimed to update the evidence regarding CA in AF patients irrespective of their baseline heart failure. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies assessing the impact of CA compared to medical regimens in AF patients with and without heart failure. Outcomes of interest were all-cause mortality, cardiovascular mortality, hospitalization for HF, hospitalization for other cardiovascular causes, and stroke. Results 13 studies were included with a total of 18370 patients. In HF patients, irrespective to their ejection fraction, CA was associated with a significant reduction in all-cause mortality (RR 0.40, 95%CI [0.37 to 0.44], cardiovascular mortality (RR 0.36, 95%CI [0.32 to 0.42]), hospitalization from HF (RR 0.65, 95%CI [0.51 to 0.82]), hospitalization from other cardiovascular causes (RR 0.71, 95%CI [0.57 to 0.89]), and the incidence of stroke (RR 0.55, 95%CI [0.50 to 0.62]). Also, six studies with a total of 2015 patients compared CA to medical treatment in AF patients with HFrEF and HFpEF. CA showed a significant reduction in all-cause mortality in HFpEF patients compared to HFrEF (RR 0.46, 95%CI [0.25 to 0.85]) with no significant differences in terms of other studied outcomes. Moreover, six studies compared CA to medical treatment in HF vs no HF with a total of 2931 patients. Patients with AF and no HF had a significant reduction in all-cause mortality (RR .041, 95%CI [0.20 to 0.80]), with no significant differences in stroke or AF recurrence. Conclusion Current evidence supports the use of catheter ablation in atrial fibrillation patients, irrespective of their baseline heart failure, to achieve lower mortality and hospitalization rates.all-cause mortalitycardiovascular mortality

Influence of donor and harvesting protocol on 30 day mortality after heart transplantation

Abstract Purpose Heart transplantation continues to be the gold standard for the treatment of advanced HF, as it promotes increased survival, exercise capacity and quality of life. The choice of the potential donor, as well as the safety of the harvesting process, graft preservation and transportation are fundamental to the success of the procedure. With the territorial extension of Brazil and a large number of donations in other states and regions, evaluating donors remotely, as well as structuring an adequate fundraising plan are fundamental. Therefore, the study of these variables and their influence on the outcome at 30 days was the objective of this study. Methods A retrospective cohort was conducted involving patients aged 18 or over, who underwent heart transplantation from July 2012 to July 2022 at our center. Patients who underwent re-transplantation and those who not used the bicaval technique were excluded. Statistical analysis was performed using STATA Software version 18. The Kaplan-Meier method was used to obtain the overall survival curve and, to identify risk factors for death, Cox proportional hazards. The Log test -rank was used for comparisons between groups. Results 255 cases of heart transplantation were studied, with a 30-day survival rate of 86.6%. The average age of donors was 29 years old and the main cause of death was traumatic brain injury.Regarding the factors that increase the risk of mortality in 30 days, the longest CPB time (HR 1.01; 95% CI 1.002-1.014; p = 0.011) and the donor's age (HR 1.08; 95% CI 1.023-1.139; p = 0.005) were statistically significant. In the univariate analysis, the donor's nutritional status (overweight or obese) was also significant (p = 0.03).The donor's length of hospital stay, use of vasoactive drugs or antimicrobials, serum sodium level or history of previous PCR did not influence the recipient's 30-day survival. Distance organ retrival surgery did not influence the outcome as long as the ischemia time of less than 240 minutes was respected. Conclusion The distance harvesting protocol used in our institution proved to be safe and effective. Adequate evaluation of the donor through echocardiography as well as management of vasoactive drugs and electrolytes may have influenced the non-relevance of classic factors that affect the outcomes of patients after heart transplantation.

Epidemiology of heart failure presentations to United States emergency departments from 2016 to 2023

IntroductionHeart failure (HF) is a common condition prompting presentation to the Emergency Department (ED) and is associated with significant morbidity and mortality. However, there is limited recent large-scale, robust data available on the admission rates, evaluation, and treatment of HF in the ED setting. MethodsThis was a cross-sectional study of ED presentations for HF from 1/1/2016 to 12/31/2023 using the Epic Cosmos database. All ED visits with ICD-10 codes corresponding to acute HF were included. We excluded congenital heart disease and isolated right-sided HF. Outcomes included percentage of total ED visits, admission rates, troponin, B-type natriuretic peptide (BNP), chest radiography, and diuretic and nitroglycerin medication administration. Subgroup analyses of medications were performed by medication and route of administration (transdermal, sublingual/oral, and intravenous). ResultsOut of 190,694,752 ED encounters, 2,626,011 (1.4 %) visits were due to acute HF. Of these, 1,897,369 (72.3 %) were admitted to the hospital. The majority of patients had a troponin (90.3 %), BNP (91.1 %), and chest radiograph (89.5 %) ordered. 82.5 % received intravenous diuresis, while 46.2 % received oral diuresis. The most common diuretic was furosemide (78.4 % intravenous, 32.5 % oral), followed by bumetanide (9.5 % intravenous, 7.1 % oral), and torsemide (0 % intravenous, 8.1 % oral). Nitroglycerin was given in 26.0 %, with the most common route being sublingual/oral (16.6 %), followed by transdermal (9.2 %) and intravenous (3.5 %). ConclusionHF represents a common reason for ED presentation, with the majority of patients being admitted. All patients received diuresis in the ED, with the majority receiving intravenous diuresis with furosemide. Approximately one-quarter received nitroglycerin with the sublingual/oral route being most common. These findings can help inform health policy initiatives, including admission decisions and evidence-based medication administration.

Therapeutic interventions for heart failure in Colombia: result of a Delphi panel.

The objective of this study was to validate the main therapies used in the treatment of heart failure through a clinical consensus conducted by cardiology experts in Colombia. The Delphi technique was employed, which involves a series of consultation rounds with experts to reach a consensus. Cardiologists with experience in HF treatment were selected, and they were sent electronic questionnaires to assess the relevance of various therapeutic interventions. Consensus was defined when at least 70% of the experts agreed on the relevance of an intervention. Fourteen cardiology experts participated in the study. In the first round, nine therapeutic interventions were evaluated, but insufficient agreement was reached to form a consensus. A second round was conducted, where feedback was provided to the experts, and they were asked to rate the relevance of the interventions using a Likert scale. Consensus was achieved for eight of the evaluated therapeutic interventions. The focus of the third round was on the interventions that had not reached consensus in the previous rounds. This study provides clinical consensus on therapeutic interventions for HF in Colombia. Nine therapeutic interventions were identified as relevant by the experts. These findings can help improve HF treatment and optimize clinical outcomes in Colombia. It is important to note that this study was conducted with local experts, and the results may not be generalizable to other populations.

Effects of SiO2 cap annealing on MOS interfaces formed on Mg-doped p-type GaN surface

In this paper, we report the effects of 800 °C SiO2 cap annealing on the Al2O3/p-type GaN (p-GaN):Mg and SiO2/p-GaN:Mg interfaces formed at relatively low temperatures, as determined by X-ray photoelectron spectroscopy (XPS) and sub-bandgap-light-assisted capacitance–voltage (C–V) measurement. For the sample with capless annealing at 800 °C and subsequent HF treatment before the Al2O3/p-GaN interface formation by atomic layer deposition at 300 °C, its C–V characteristics indicated the existence of high-density midgap states. By SiO2 cap annealing and subsequent HF treatment to remove the cap layer, we found that the Al2O3/p-GaN interface showed a reduction in midgap state density. The same effect was confirmed at the SiO2/p-GaN interface. Taking this finding and XPS results together, we consider the possibility that SiO2 cap annealing at 800 °C and the subsequent HF treatment prior to the formation of the Al2O3/p-GaN and SiO2/p-GaN interfaces led to the reduction of interface disorder.

Whole-body mass spectrometry imaging reveals the systemic metabolic disorder and catecholamines biosynthesis alteration on heart-gut axis in heart failure rat

IntroductionHeart failure (HF) is a systemic metabolic disorder disease, across multiorgan investigations advancing knowledge of progression and treatment of HF. Whole-body MSI provides spatiotemporal information of metabolites in multiorgan and is expected to be a potent tool to dig out the complex mechanism of HF. ObjectivesThis study aimed at exploring the systemic metabolic disorder in multiorgan and catecholamines biosynthesis alteration on heart-gut axis after HF. MethodsWhole-body MSI was used to characterize metabolic disorder of the whole rat body after HF. An integrated method by MSI, LC-MS/MS and ELISA was utilized to analyze key metabolites and enzymes on heart, small intestine, cecum and colon tissues of rat. Gut microbiota dysbiosis was investigated by 16S rDNA sequencing and metagenomic sequencing. Validation experiments and in vitro experiments were performed to verify the effect of catecholamines biosynthesis alteration on heart-gut axis after HF. ResultsWhole-body MSI exhibited varieties of metabolites alteration in multiple organs. Remarkably, catecholamine biosynthesis was significantly altered in the serum, heart and intestines of rats. Furthermore, catecholamines and tyrosine hydroxylase were obviously upregulated in heart and colon tissue. Turicibacter_sanguinis was relevant to catecholamines of heart and colon. Validation experiments demonstrated excessive norepinephrine induced cardio-intestinal injury, including significantly elevating the levels of BNP, pro-BNP, LPS, DAO, and increased the abundance of Turicibacter_sanguinis. These alterations could be reversed by metoprolol treatment blocking the effect of norepinephrine. Additionally, in vitro studies demonstrated that norepinephrine promoted the growth of Turicibacter_sanguinis and Turicibacter_sanguinis could import and metabolize norepinephrine. Collectively, excessive norepinephrine exerted bidirectional effects on cardio-intestinal function to participate in the progression of HF. ConclusionOur study provides a new approach to elucidate multiorgan metabolic disorder and proposes new insights into heart-gut axis in HF development.

Repair Bond Strength of Composite Resin to Dental Ceramic Using Various Surface Treatments: An In Vitro Study

Abstract Aim: This research aims to evaluate and compare the effect of various surface treatments and adhesive types on the bond strength between composite resin and two types of ceramic materials. Materials and Methods: A total of 98 disk-shaped of 10 mm diameter and 4 mm thickness were fabricated for each of the zirconia (H. C. Starck) and lithium disilicate (IPS E-Max computer-aided design), which were implanted individually in the acrylic resin mold leaving one surface exposed. The disks in each group were sub-divided according to the surface treatments into seven groups (n = 14): [hydrofluoric acid (HF, 9.5%), air abrasion, bur, laser, HF + bur, HF + air abrasion, HF + laser]. Each sub-group was further divided into two groups (n = 7) according to the type of adhesive used for the repairing procedure [G-Premio Bond universal adhesive group and intraoral repair kit (BISCO) group]. Each adhesive was applied depending on manufacturer instructions and, then, the composite cylinder (4 mm in diameter and 4 mm in height) was built on the pre-determined treated ceramic surface area by the addition of rubber mold. Then the samples were stored in distal water for 24 h. After that, all groups were submitted to a shear bond test using an Instron testing machine (TSTM 02500; Elista Ltd., Istanbul, Turkey) at 0.5 mm/min a crosshead speed. The data were analyzed by three-way analysis of variance and Tukey post hoc test at (P ≤ 0.05). Results: The HF + air abrasion groups registered the higher bond strength but with no statistically significant difference from groups of HF + bur. While the laser groups showed the lowest mean bond strength. Generally, E-Max registered significantly higher bond strength in comparison to zirconia. Finally, the BISCO repair system registered a significantly higher bond strength value in comparison to G-Premio. Conclusion: Combined surface treatment of HF + air abrasion with an intraoral repair kit can provide a promising method for repairing cracked ceramic restorations. However, repairing lithium disilicate is more predictable and successful than zirconia.

Jiawei Taohe Chengqi Decoction attenuates CCl4 induced hepatic fibrosis by inhibiting HSCs activation via TGF-β1/CUGBP1 and IFN-γ/Smad7 pathway

BackgroundHepatic fibrosis (HF) is an essential stage in the progression of different chronic liver conditions to cirrhosis and even hepatocellular carcinoma. The activation of hepatic stellate cells (HSCs) plays a crucial role in the progression of HF. IFN- γ/Smad7 pathway can inhibit HSCs activation, while TGF-β1/CUGBP1 pathway can inhibit IFN-γ/Smad7 pathway transduction and promote HSCs activation. Thus, inhibiting the TGF-β1/CUGBP1 pathway and activating the IFN-γ/Smad7 pathway reverses HSCs activation and inhibits HF. Jiawei Taohe Chengqi Decoction (JTCD) was derived from the Taohe Chengqi Tang in the ancient Chinese medical text titled “Treatise on Febrile Diseases”. We found several anti-HF components in JTCD including ginsenoside Rb1 and others, but the specific mechanism of anti-HF in JTCD is not clear. PurposeTo elucidate the specific mechanism by which JTCD reverses HF by inhibiting the activation of HSCs, and to establish a scientific foundation for treating HF with Traditional Chinese medicine (TCM). MethodsWe constructed a CCl4-induced mice HF model in vivo and activated human hepatic stellate cell line (LX-2) with TGF-β1 in vitro, after which they were treated with JTCD and the corresponding inhibitors. We examined the expression of pivotal molecules in the two pathways mentioned above by immunofluorescence staining, Western blotting and RT-PCR. ResultsJTCD attenuated liver injury and reduced serum ALT and AST levels in mice. In addition, JTCD attenuated CCl4-induced HF by decreasing the expression of α-SMA, COL1A1 and other markers of HSCs activation in mice liver tissue. Moreover, JTCD effectively suppressed the levels of TGF-β1, p-Smad3, p-p38MAPK, p-ATF2, and CUGBP1 in vivo and in vitro and upregulated the levels of IFN-γ, p-STAT1, and Smad7. Mechanically, after using the inhibitors of both pathways in vitro, we found that JTCD inhibited the activation of HSCs by restoring the balance of the TGF-β1/CUGBP1 and IFN-γ/Smad7 pathways. ConclusionWe demonstrated that JTCD inhibited HSCs activation and reversed HF by inhibiting the TGF-β1/CUGBP1 signalling pathway and upregulating the IFN-γ/Smad7 signalling pathway. Moreover, we have identified specific links where JTCD interferes with both pathways to inhibit HSCs activation. JTCD is an effective candidate for the clinical treatment of HF.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components

BackgroundHeart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. MethodsThe active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model.ResultsWe initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated.ConclusionsMechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.Graphical

Risk of Atrial Fibrillation Induced by Ivabradine in Correlation with Left Atrial Size

Abstract Background Ivabradine (Procoralan, Servier) is a heart rate lowering drug which acts by specifically inhibiting the pacemaker If current, which causes spontaneous depolarization in the sino-atrial node that regulates the heart rate. Objective To correlate Left atrial size with development of AF in patients treated with ivabradine over a 12 week period. Patients and Methods Our study was conducted upon 180 patients referred to Ain Shams University Hospital and Misr University for Science and Technology hospital, from September 2020 to February 2021 to undergo treatment for HF or IHD with the appropriate medications with AF being the primary outcome of interest and how it correlates with Ivabradine therapy. Results Our results showed that there was no statistically significant difference between the two groups regarding the incidence of AF (p = 0.587). Likewise, there was no statistically significant difference between the two groups regarding duration till AF at 1st month, 2nd month and 3rd month (p > 0.05). This could be explained by the lower number of patients included in the study as compared to other similar studies. When the entire patient population who developed AF was pooled regardless of their Ivabradine use, there was a statistically significant increase in AF incidence with larger left atrial volume indices. Conclusion In the present study, Ivabradine treatment was not associated with a higher incidence of AF in patients with heart failure and/or ischemic heart disease. Also, there was no significant difference in the duration until AF occurrence when it was evaluated at the end of the 1st, 2nd, and 3rd months. Higher LAVI was associated with a higher incidence of AF in the total studied patient population regardless of Ivabradine use.

LTBP2 Knockdown Ameliorates Cardiac Fibrosis and Apoptosis via Attenuating NF‐κB Signaling Pathway and Oxidative Stress in Mice with Cardiac Hypertrophy

AbstractAt present, there is no therapeutic approach available to reverse the progression of pathological fibrosis and ventricle chamber stiffening. This study is designed to explore the effects of latent transforming growth factor‐beta‐binding protein 2 (LTBP2) on cardiac fibrosis in hypertrophic cardiomyopathy and the underlying mechanisms. The key differential gene LTBP2 is identified by mRNA sequencing. Ang II‐induced cells and mice are treated with LTBP2 si‐RNA or knockdown adenovirus, respectively, and the indicators of cardiac function, oxidative stress, cardiac fibrosis, apoptosis, and remodeling are examined. The underlying mechanism is elucidated in vitro by oxidative stress and an agonist of nuclear factor‐kappa B (NF‐κB). LTBP2 is upregulated in the cardiac tissue of mice with Ang II‐mediated HF. The knockdown of LTBP2 enhanced cardiac function, attenuated cardiac fibrosis, apoptosis, hypertrophy, and oxidative stress injury, and suppressed NF‐κB expression. These results are validated in vitro. The effects of LTBP2 gene silencing are reversed by either NF‐κB or oxidative stress agonists in vitro. Taken together, these findings suggest that LTBP2 knockdown alleviates HF by inhibiting cardiac fibrosis, apoptosis, and hypertrophy via attenuating NF‐κB signaling pathway and oxidative stress. Thus, targeting LTBP2 may be a novel approach to the treatment of HF.

Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism

BackgroundHeart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism.Methods In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated.ResultsIn both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism.ConclusionsXBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

HEART FAILURE WITH RELAPSING ATRIAL FIBRILLATION: BELOW THE SURFACE

Abstract Advances in pharmacologic and device therapy have greatly improved prognosis of patients with HFrEF. However, the typical clinical course is still characterized by recurring symptoms, worsening functional status and risk of frequent hospitalizations. A 72–years–old male patient with arterial hypertension, poorly controlled T2DM, TIA and chronic kidney disease presented to Cardiology service in 2018 with dyspnoea on effort and first evidence of EF 35% at echocardiography. He was admitted for elective coronary angiography, which demonstrated limited coronary heart disease of circumflex artery and its first marginal branch, treated by PTCA and stenting. CMR confirmed severe LV dysfunction, but also revealed extensive fibrotic areas with ischaemic and non–ischaemic patterns beyond revascularized regions. With such evidences, HF treatments were intensified, with titration of disease– modifying therapies and DOAC was added for asymptomatic paroxysmal AF. CRT–D was implanted for QRS of 160 msec, which was narrowed to 130 msec. Nevertheless, in one–year time the patient presented worsening of symptoms with several hospital admissions for acute HF and AF with fast rate. A switch to rhythm–control strategy was hence chosen. DCCV was performed, after an initial deferral for thrombosis of LAA due to poor adherence to DOAC. However, three–days after DCCV, the patient presented again to emergency services for dyspnoea, left upper flank pain and AF with fast rate. He was admitted to Acute Medicine Unit and treated with high flow O2, iv Furosemide and Digoxin, analgesics. CT chest and abdomen with contrast was performed in the suspicion of systemic venous thromboembolism for persistent type 1 respiratory failure, raised D–dimer and elevated liver function tests, despite appropriate anticoagulation. CT revealed an unexpected left superior pulmonary vein thrombosis, splenic and small left renal infarcts. The patient was discharged after recovery on subcutaneous heparin. At 15–day review, the patient was in stable conditions and awaiting completion of coagulation screening tests. This case study addresses some important aspects in the care of HF. An accurate assessment of HF aetiology and recurrent triggers, a timely planning of pharmacologic and device treatments, alongside with management of co–morbidities, therapeutic adherence and appropriate anticoagulation, can provide the clinician powerful tools to accomplish the difficult task of managing HF below the surface.

Factors affecting hospitalization and mortality in a retrospective study of elderly patients with heart failure

BackgroundHeart failure (HF) has a high prevalence in an elderly population and leads to a substantial hospitalization and mortality. The objective of this study was to investigate factors that affect hospitalization and mortality in an elderly population.MethodsA retrospective observational study was conducted of HF patients aged 76–95 years residing in Region Halland, Sweden. Between 2013 and 2019, a total of 3134 patients received a novel diagnosis of HF and were subsequently monitored for one year using data from a healthcare database. The patients were categorized into HF-phenotypes according to ejection fraction (EF) and those with HF diagnose solely based on clinical criteria with no defined EF. Cox regression analysis for hospital admissions and mortality was evaluated adjusted for pharmacotherapies, healthcare utilization and clinical characteristics.ResultsEchocardiogram was performed in 56% of the patients and 51% were treated with recommended HF pharmacotherapy with betablockers combined with renin-angiotensin-aldosterone-system inhibition. The average number of inpatient days was 10.7 while the average number of visits to primary care physician was 5.4 and 8.7 to primary care nurse respectively. A Cox regression analysis for hospital admissions and mortality revealed that an eGFR < 30 ml/min was associated with a hazard ratio (HR) of 1.88 (confidence interval [CI] 1.56–2.28), elevated NT-proBNP with an HR of 2.09 (CI 1.59–2.76), diabetes with an HR of 1.31 (CI 1.13–1.52), and chronic obstructive pulmonary disease with an HR of 1.51 (CI 1.29–1.77). Having a primary care physician visit was associated to an HR of 0.16 (CI 0.14–0.19), and the use of recommended heart failure pharmacotherapy was associated with an HR of 0.52 (CI 0.44–0.61).ConclusionsIn a Swedish elderly population with HF, factors such as advancing age, kidney dysfunction, elevated NT-proBNP levels, diabetes, and COPD were associated with an increased risk of both mortality and hospitalization. Conversely, patients who received recommended heart failure treatment and made regular visits to their primary care physician were associated with a decreased risk. This indicates that elderly patients with HF benefit from recommended HF treatment and highlights that follow-ups in primary care could be advantageous.

Mortality Benefit Among Primary Prevention Implantable Cardioverter-Defibrillator Recipients on Contemporary Heart Failure Treatment

BackgroundPast clinical trials have shown the benefit of implantable cardioverter-defibrillators (ICDs) for reducing sudden cardiac death in at-risk patients. However, heart failure management and ICD technology have changed since these trials were first published. An updated assessment of ICD mortality benefit is needed. ObjectivesThe purpose of this study was to compare mortality rates between patients with a primary prevention (PP) indication for an ICD who did or did not receive an ICD using a contemporary, real-world data set. MethodsData was obtained from a large electronic health record data set covering patients in the United States from 2012 through 2020 who had a PP indication for an ICD and survived at least 1-year postindication. ResultsA total of 25,296 patients were identified as having a PP indication for ICD implantation, of which 2,118 (8.4%) were treated with an ICD within a year. Treated patients were younger than nontreated patients (age 63.4 years vs 66.1 years) with a smaller proportion of women (25.0% vs 36.7%). After 4-to-1 propensity matching, treated patients had similar clinical characteristics to nontreated patients. A Cox proportional hazard model estimated a 24.3% lower risk of all-cause mortality in patients when treated vs not treated with an ICD (HR: 0.757; 95% CI: 0.678-0.835; P <0.001). There was no detectable difference in ICD benefit between patients with ischemic and nonischemic heart disease (P = 0.50). ConclusionsICD treatment of patients with a PP indication is associated with improved mortality even in the context of evolving adjunctive HF treatment, consistent with earlier landmark trials.

Network pharmacology and molecular docking analysis on Shenfu Qiangxin indicate mTOR is a potential target to treat heart failure

BackgroundHeart failure (HF) is one of the major causes of mortality worldwide with high recurrence rate and poor prognosis. Our study aimed to investigate potential mechanisms and drug targets of Shenfu Qiangxin (SFQX), a cardiotonic-diuretic traditional Chinese medicine, in treating HF.MethodsAn HF-related and SFQX-targeted gene set was established using disease-gene databases and the Traditional Chinese Medicine Systems Pharmacology database. We performed gene function and pathway enrichment analysis and constructed protein–protein interaction (PPI) network to investigate the potential mechanisms. We also performed molecular docking to analyze the interaction patterns between the active compounds and targeted protein.ResultsA gene set with 217 genes was identified. The gene function enrichment indicated that SFQX can regulate apoptotic process, inflammatory response, response to oxidative stress and cellular response to hypoxia. The pathway enrichment indicated that most genes were involved in PI3K–Akt pathway. Eighteen hub target genes were identified in PPI network and subnetworks. mTOR was the key gene among hub genes, which are involved in PI3K–Akt pathway. The molecular docking analysis indicated that 6 active compounds of SFQX can bind to the kinase domain of mTOR, which exerted potential therapeutic mechanisms of SFQX in treating HF.ConclusionsThe results of network pharmacology analysis highlight the intervention on PI3K–Akt pathway of SFQX in the treatment of HF. mTOR is a key drug target to help protect myocardium.