A Rare Case of Primary Malignant Pericardial Mesothelioma Diagnosed with Pericardiotomy.

Primary malignant pericardial mesothelioma (PMPM) is an extremely rare and lethal cardiac tumor. This article presents a 62-year-old man with recurrent pericardial fluid. The patient's clinical symptoms and imaging features were nonspecific. Initial diagnosis was constrictive pericarditis. After admission, the patient's symptoms worsened, and echocardiography indicated increased pericardial effusion. To diagnose and improve the patient's symptoms, pericardiotomy was performed; however, the procedure was unsuccessful because the pericardium was densely adherent to the myocardium. Histopathological examination, including immunohistochemical staining of the pericardial specimen revealed malignant mesothelioma. We recommended adjuvant therapy for the patient with cis-platinum and pemetrexed; however, the patient and his family refused treatment. The patient was discharged 11 days after surgery. The patient survived for more than 15 months with surgical treatment. In this report, the patient's symptoms improved, and the patient survived beyond the median survival after surgical treatment.   Conclusion: The definitive diagnosis of PMPM mostly has been obtained from specimens obtained by surgery. Surgery is an effective treatment method because it prevents cardiac tamponade and can improve symptoms or prognosis, but complete resection is impossible.

Circulating monocytes accelerate acute liver failure by IL-6 secretion in monkey.

Acute liver failure (ALF) is associated with high mortality, and a poor understanding of the underlying pathophysiology has resulted in a lack of effective treatments so far. Here, using an amatoxin-induced rhesus monkey model of ALF, we panoramically revealed the cellular and molecular events that lead to the development of ALF. The challenged monkeys with toxins underwent a typical course of ALF including severe hepatic injury, systemic inflammation and eventual death. Adaptive immune was not noticeably disturbed throughout the progress of ALF. A systematic examination of serum factors and cytokines revealed that IL-6 increase was the most rapid and drastic. Interestingly, we found that IL-6 was mainly produced by circulating monocytes. Furthermore, ablation of monocyte-derived IL-6 in mice decreased liver injury and systemic inflammation following chemical injection. Our findings reveal a critical role of circulating monocytes in initiating and accelerating ALF, indicating a potential therapeutic target in clinical treatment for ALF.

Salidroside Protects Against Advanced Glycation End Products-Induced Vascular Endothelial Dysfunction.

BACKGROUND Salidroside, the major active compound in Rhodiola, has been reported to provide beneficial effects on cardiovascular diseases, but its effects on diabetes-induced vascular endothelial dysfunction are less known. Here, we examined the protective effects of salidroside on endothelial function in diabetes and explored the potential underlying mechanism. MATERIAL AND METHODS First, we assessed the endothelium-dependent relaxation response to acetylcholine, with or without salidroside treatment, in aortas isolated from Sprague-Dawley rats. Then, cell viability, oxidative biomarkers, and protein expression were tested to determine the effect of salidroside treatment on human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS Advanced glycation end product (AGE)-induced endothelial dysfunction was significantly improved by salidroside treatment (P<0.05), as shown by a reduced relaxation response to the vasodilator acetylcholine. Further, incubation with salidroside restored NO levels and reduced reactive oxygen species formation in AGE-stimulated HUVECs in a concentration-dependent manner (P<0.05). We also showed that nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor kappa B (NF-κB) signaling was critical for the salidroside-mediated beneficial regulation. CONCLUSIONS Our results demonstrate that salidroside protects against AGE-induced endothelial dysfunction, and its effects may be in part attributed to the induction of HO-1 and attenuation of phosphorylated NF-κB p65.

Evaluation of P wave Dispersion and Tissue Doppler Imaging for Predicting Paroxysmal Atrial Fibrillation in Patients with Hypertension.

BACKGROUND: There are no previous studies dealing with paroxysmal atrial fibrillation (AF) and hypertension using electrocardiogram and tissue doppler imaging (TDI). The aim of this study was to investigate and identify the predictive indicators for paroxysmal AF in hypertensive patients using P wave dispersion (Pd) and TDI. METHODS: Patients with hypertension were enrolled. Patients with paroxysmal AF were classified as the PAF group, and patients without a history of paroxysmal AF were classified as the NAF group. The clinical data, P wave indicators and TDI indicators were collected and compared between the two groups. RESULTS: A total of 120 patients were enrolled into the study with 40 cases in the PAF group and 80 cases in the NAF group. Compared with NAF group, Pd, maximum P wave duration (Pmax), left ventricular end-diastolic dimension (LVEDd) and left atrial dimension (LAD) were significantly longer (P < .05) in the PAF group. PAL, PAI, PAR, LR, LI and IR were significantly longer (P < .05) in the PAF group than in the NAF group. As for ROC analysis, Pd and PAL had the greatest area under the curve. The best diagnostic value of Pd and PAL was 40ms and 78ms, respectively. The combination of Pd ≥40ms with Pmax ≥ 110ms showed higher specificity and positive predictive value but decreased sensitivity and negative predictive value for paroxysmal AF. CONCLUSIONS: The PAF group had significantly longer atrial electromechanical time and higher Pd compared with NAF group. The combination of Pd and TDI may be helpful to predict the onset of paroxysmal AF in patients with hypertension.

Salidroside protects against foam cell formation and apoptosis, possibly via the MAPK and AKT signaling pathways.

BACKGROUND: Foam cell formation and apoptosis are closely associated with atherosclerosis pathogenesis. We determined the effect of salidroside on oxidized low-density lipoprotein (ox-LDL)-induced foam cell formation and apoptosis in THP1 human acute monocytic leukemia cells and investigated the associated molecular mechanisms. METHODS: THP1-derived macrophages were incubated with salidroside for 5 h and then exposed to ox-LDL for 24 h to induce foam cell formation. Cytotoxicity, lipid deposition, apoptosis, and the expression of various proteins were tested using the CCK8 kit, Oil Red O staining, flow cytometry, and western blotting, respectively. RESULTS: Ox-LDL treatment alone promoted macrophage-derived foam cell formation, while salidroside treatment alone inhibited it (p < 0.05). The number of early/late apoptotic cells decreased with salidroside treatment in a dose-dependent manner (p < 0.05). Salidroside dramatically upregulated nuclear factor erythroid 2-related factor 2, but had no effect on heme oxygenase-1 expression; moreover, it markedly downregulated ox-LDL receptor 1 and upregulated ATP-binding cassette transporter A1. Salidroside also obviously decreased the phosphorylation of JNK, ERK, p38 MAPK, and increased that of Akt. However, the total expression of these proteins was not affected. CONCLUSION: Based on our findings, we speculate that salidroside can suppress ox-LDL-induced THP1-derived foam cell formation and apoptosis, partly by regulating the MAPK and Akt signaling pathways.

Protective Effects of Colivelin Against Alzheimer's Disease in a PDAPP Mouse Model.

BACKGROUND: Alzheimer's disease (AD) is characterized with progressive memory loss and severe cognitive impairments, which affect everyday life and human health in the elderly. It is required that an effective and safe protective reagent against AD should be developed. It has been reported that humanin (HN) exerts neuroprotective effects against AD. In this study, we investigated the effect of a novel and more effective HN derivative, Colivelin (CLN) on AD. METHODS: PDAPP(V717I) transgenic AD model mice (derived from parental C57/BL6 mice) were used in our study as AD model. Morris water maze test was used to test the memory impairment of AD mice and the levels of Aß40 and Aß42 were determined by an Elisa assay. We used an Immunohistochemistry and Immunofluorescence staining method to check the GFAP and MAP2 positive cells, and TUNEL to assess the apoptotic cells. Western blot assay was used to check the expression and phosphorylation level of p38. RESULTS: We found that CLN improved the memory impairment induced by AD and reduced the deposit of Aß40 and Aß42. CLN also inhibited cell apoptosis and activation of caspase 3 in brain tissues of AD mice. Inflammation in AD mice was alleviated by CLN treatment, including the accumulation of GFAP positive cells and the inflammatory cytokines. With both structure of AGA-HNG and ANDF, CLN exhibited significantly stronger effects than synchronously administration of AGA-HNG and ADNF, suggesting CLN as a novel potential effective therapeutic reagent for AD patients. Finally, we found that CLN inhibited phosphorylation of p38 in AD mice and p38 inhibitor, SB203580 weakened the therapeutic effect of CLN. CONCLUSION: CLN effectively improved the memory dysfunction in PDAPP mice, and our data suggests CLN as a novel and effective reagent which may have great potentials in AD therapy.

Random discrete linear canonical transform.

Linear canonical transforms (LCTs) are a family of integral transforms with wide applications in optical, acoustical, electromagnetic, and other wave propagation problems. In this paper, we propose the random discrete linear canonical transform (RDLCT) by randomizing the kernel transform matrix of the discrete linear canonical transform (DLCT). The RDLCT inherits excellent mathematical properties from the DLCT along with some fantastic features of its own. It has a greater degree of randomness because of the randomization in terms of both eigenvectors and eigenvalues. Numerical simulations demonstrate that the RDLCT has an important feature that the magnitude and phase of its output are both random. As an important application of the RDLCT, it can be used for image encryption. The simulation results demonstrate that the proposed encryption method is a security-enhanced image encryption scheme.

Quantification of endothelial microparticles on modified cytometric bead assay and prognosis in chest pain patients.

BACKGROUND: Endothelial microparticles (EMPs) are vehicles released from activated or apoptotic endothelium. The aim of this study was to establish a new cytometric bead assay for EMPs and investigate the prognostic value of EMPs in chest pain patients. METHODS AND RESULTS: We invented and verified the cytometric bead assay to quantify EMP level in vitro. A total of 80 healthy volunteers and 350 chest pain patients were recruited and the EMPs measured. The major adverse cardiovascular events (MACE) of documented coronary artery disease patients were recorded in the follow-up period. The level of EMPs statistically correlated with those of endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) in vitro. The EMP level in healthy subjects was <300.10. The patients had a remarkably higher EMP level than healthy subjects. Diabetes mellitus, EMP, and ET-1 levels were significantly associated with future cardiovascular events in chest pain patients. There was a significantly higher event incidence in the top tertile EMP level than in the lower tertile in the acute coronary syndrome (ACS) patient group. CONCLUSIONS: A novel EMP quantification assay has been successfully established. The EMPs in vitro and in patients were significantly correlated with ET-1 and ICAM-1 level. The patients with a higher EMP level had a higher risk of MACE. EMP level is a predictor for MACE in ACS patients.

Elevated plasma level of pentraxin-3 predicts in-hospital and 30-day clinical outcomes in patients with non-ST-segment elevation myocardial infarction who have undergone percutaneous coronary intervention.

OBJECTIVES: This investigation explored the short-term prognostic value of pentraxin-3 (PTX3) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated by percutaneous coronary intervention (PCI). METHODS: We measured plasma levels of PTX3 and other biomarkers in 525 PCI-treated NSTEMI patients (mean age, 57.7 years; 328 males). The associations of PTX3 levels with cardiac events and cardiac deaths occurring within 30 days of discharge were evaluated with multivariable Cox proportional hazard models. RESULTS: Renal function, diabetes prevalence, systolic blood pressure, heart rate and ejection fraction differed significantly in the high PTX3 (≥3.0 ng/ml, n = 107) and low PTX3 (<3.0 ng/ml, n = 418) groups (all p < 0.05). Plasma PTX3 levels were correlated with high-sensitivity C-reactive protein, troponin T and N-terminal pro-B-type natriuretic peptide in NSTEMI patients (all p < 0.05). Kaplan-Meier analysis showed in-hospital and 30-day cardiac events and deaths were higher in the high PTX3 group (both p < 0.01). Elevated PTX3 was an independent predictor of 30-day cardiac events (95% CI 1.09-1.68; p = 0.006) and mortality (95% CI 1.18-2.15; p = 0.002). CONCLUSIONS: An elevated plasma level of PTX3 predicts 30-day cardiac events and mortality in PCI-treated NSTEMI patients.

Cardiopulmonary exercise test combined with red blood cell distribution width to predict cardiovascular complication of thoracic surgery.

Cardiovascular complications in patients undergoing thoracic surgery, which physicians have a limited ability to predict, are often unavoidable and resulting in adverse outcome. Cardiopulmonary exercise testing (CPET), the gold standard of cardiopulmonary function evaluation, has also been proved to be a preoperative risk assessment tool. Meanwhile, elevated red blood cell distribution width (RDW) has surged as a biochemical marker in the occurrence of cardiovascular disease. However, it is yet unclear the value of CPET combined with RDW in predicting cardiovascular complications after thoracic surgery. 50 patients with cardiovascular complications after thoracic surgery were collected as the case group, and 100 thoracic surgery patients were recruited as the control group, with the same gender, age ± 2 years old, and no postoperative complications. After admission, all patients underwent CPET and RDW inspection before surgery, and the results were recorded. The CPET parameter oxygen pulse (VO2/HR) and RDW of the case group were lower than those of the control group (P < 0.05), and the ventilation/carbon dioxide production (VE/VCO2 slope) was significantly higher than control group (P < 0.01). The biochemical parameters hemoglobin (Hb) and Glomerular filtration rate (GFR)) of the case group were lower than those of the control group (P < 0.05), the homocysteine (hCY), creatinine (Cr), operation time and blood loss of the case group were higher than those of the control group (P < 0.05). The RDW had a negative correlation with VO2 max in both overall and control group. The combination of VO2/kg and RDW had the highest diagnostic value in predicting cardiovascular complications. The combination of VO2/kg and RDW has predictive diagnostic value and is more suitable for predicting postoperative complications of thoracic surgery.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

ECM-inspired calcium/zinc laden cellulose scaffold for enhanced bone regeneration.

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.

Dynamics of The Γδtcr Repertoires During The Dedifferentiation Process and Pilot Implications for Immunotherapy of Thyroid Cancer.

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies.

New Clues to Cardiovascular Disease: Erythrocyte Lifespan.

Determination of erythrocyte lifespan is an important part of the diagnosis of hemolytic diseases. Recent studies have revealed alterations in erythrocyte lifespan among patients with various cardiovascular diseases, including atherosclerotic coronary heart disease, hypertension, and heart failure. This review summarizes the progress of research on erythrocyte lifespan in cardiovascular diseases.

Pulmonary artery sarcoma misdiagnosed as a pulmonary embolism: A case report.

Pulmonary artery sarcoma is a rare type of tumor and is easily misdiagnosed. We report a case of pulmonary artery sarcoma in a 26-year-old young man who presented with acute onset of dyspnea. Computed tomographic angiography of the chest had revealed a large filling defect within the main pulmonary artery (PA) that extended into both right and left PAs. Because pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, leading to the resection of the mass. After an uneventful postoperative course, the patient was discharged from the hospital on postoperative day ten. He was subsequently treated with chemotherapy and continued to show no evidence of disease. Multimodal therapy can provide prolonged survival.

Taxifolin ameliorates abdominal aortic aneurysm by preventing inflammation and apoptosis and extracellular matrix degradation via inactivating TLR4/NF-κB axis.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a serious aortic disease with high mortality. Vascular smooth muscle cells (VSMCs) loss is a prominent feature of AAA. Taxifolin (TXL) is a natural antioxidant polyphenol and possesses therapeutic functions in numerous human diseases. This study aimed to investigate TXL's impact on VSMC phenotype in AAA. METHODS: In vitro and in vivo of VSMC injury model was induced by angiotensin II (Ang II). The potential function of TXL on AAA was determined using Cell Counting Kit-8, flow cytometry, Western blot, quantitative reverse transcription-PCR, and enzyme-linked immunosorbent assay. Meanwhile, TXL mechanism on AAA was checked by a series of molecular experiments. Also, TXL function on AAA in vivo was further evaluated using hematoxylin-eosin staining, TUNEL assay, Picric acid-Sirius red staining and immunofluorescence assay in C57BL/6 mice. RESULTS: TXL alleviated Ang II-induced VSMC injury mainly by enhancing VSMC proliferation and weakening cell apoptosis, alleviating VSMC inflammation, and reducing extracellular matrix (ECM) degradation of VSMCs. Furthermore, mechanistic studies corroborated that TXL reversed the high levels of Toll-like receptor 4 (TLR4) and p-p65/p65 induced by Ang II. Also, TXL facilitated VSMC proliferation and reduced cell apoptosis, repressed inflammation, and ECM degradation of VSMCs, while these effects were reversed by TLR4 overexpression. In vivo studies further confirmed that TXL owned the function of alleviating AAA, such as alleviating collagen fiber hyperplasia and inflammatory cell infiltration in AAA mice, and repressing inflammation and ECM degradation. CONCLUSION: TXL protected VSMCs against Ang II-induced injury through activating TLR4/noncanonical nuclear factor-kappaB(NF-κB).

FOXP1­induced DUSP12 alleviates vascular endothelial cell inflammation and oxidative stress injury induced by ox­LDL via MAP3K5 signaling pathway.

Atherosclerosis (AS) is a type of chronic inflammatory disease and the main pathological basis of cardiovascular and cerebrovascular diseases, which seriously threaten the health of patients. The dual specificity phosphatase 12 (DUSP12) protein is known as regulator of inflammatory diseases. Nonetheless, at present, there are only a few reports on the regulatory role of DUSP12 in AS. Human umbilical vein endothelial cells (HUVECs) were induced using oxidized low-density lipoprotein (ox-LDL). Subsequently, cell transfection experiments were performed to overexpress DUSP12 in ox-LDL-induced HUVECs. Cell Counting Kit-8, TUNEL western blotting, 2',7'-dichlorofluorescein diacetate assays, ELISA and other techniques were used to measure cell viability, apoptosis, inflammation, oxidative stress and endothelial function-related indicators. Subsequently, the relationship between DUSP12 and Forkhead box P1 (FOXP1) was predicted using the JASPAR database and verified using luciferase reporter and chromatin immunoprecipitation assays. Finally, the regulatory mechanism was investigated by simultaneously overexpressing DUSP12 and knocking down FOXP1 in ox-LDL-induced HUVECs and MAP3K5-related proteins of the DUSP12 downstream pathway were measured by western blotting. The expression of DUSP12 in ox-LDL-induced HUVECs was significantly decreased. Overexpression of DUSP12 inhibited apoptosis, inflammation and oxidative stress damage and alleviated endothelial dysfunction in ox-LDL-induced HUVECs. FOXP1 promoted the transcription of DUSP12. Moreover, FOXP1 alleviated ox-LDL-induced apoptosis, inflammation and oxidative stress damage in HUVECs by regulating the expression of DUSP12, probably acting through the MAP3K5 pathway. Collectively, the present study revealed that FOXP1-induced DUSP12 alleviated vascular endothelial cell inflammation and oxidative stress injury in ox-LDL-induced HUVECs via the MAP3K5 signaling pathway, which might shed novel insights into the targeted treatment for AS in the clinic.

ΔRDW Could Predict Major Adverse Cardiovascular Events in Patients with Heart Failure with Reduced Ejection Fraction After Sacubitril/Valsartan Treatment.

Objective: This study aimed to evaluate the association between red blood cell distribution width (RDW) changes and major adverse cardiovascular event (MACE) occurrences during sacubitril/valsartan treatment in patients with heart failure with reduced ejection fraction (HFrEF). Methods: This study retrospectively analyzed the medical records of patients with HFrEF hospitalized from April 2018 to February 2021. The patients were divided into two groups according to the inclusion of sacubitril/valsartan in the personal drug treatment regimen, the traditional and the sacubitril/valsartan group. RDW values before and after sacubitril/valsartan treatment were recorded respectively as RDW1 and RDW2. ΔRDW was defined as the difference between RDW2 and RDW1. The patients in the sacubitril/valsartan group were divided into two subgroups according to ΔRDW >0 or ≤0. MACEs, such as readmission for HF, acute myocardial infarction, ischemic stroke, and malignant arrhythmia and death, were recorded during the 1-year follow-up period in each group. Results: MACE development was lower in patients treated with sacubitril/valsartan than those treated with conventional therapy (log-rank, P<0.001). The incidence of cardiac events during the follow-up period was greater in the group with ΔRDW >0 than in the group with ΔRDW ≤0 (Breslow, P<0.001). Increased RDW was associated with a higher likelihood of developing MACE than decreased RDW (odds ratio [OR] =2.055, 95% confidence interval [CI]:1.301-3.246), and the risk of developing MACE increased by 22.1% for each unit increase in RDW (OR=1.221, 95% CI:1.074-1.389). Conclusion: Sacubitril/valsartan treatment is effective in reducing the risk of MACEs in HFrEF. Additionally, RDW changes are predictors of MACEs after sacubitril/valsartan treatment.

Combined treatment with sacubitril/valsartan plus dapagliflozin in patients affected by heart failure with reduced ejection fraction.

Background: Data about real-world effects of combined therapy with sacubitril/valsartan plus dapagliflozin in patients affected by heart failure (HF) with reduced ejection fraction (HFrEF) has not been widely reported. In this article, the benefits of dapagliflozin and sacubitril/valsartan respect to improvements of cardiac function in patients with HFrEF would be investigated. Methods: HF patients prescribed sacubitril/valsartan between January 2020 and January 2022 in a tertiary teaching hospital were selected using the Computerized Patient Record System. Patients were divided into two groups according to whether they were taking dapagliflozin. Clinical parameters at baseline and during follow-up were retrospectively collected and analyzed. Results: Total of 136 consecutive patients were recruited for this study. 72 patients treated with sacubitril/valsartan and dapagliflozin were assigned to Group A, and another 64 patients receiving sacubitril/valsartan monotherapy were assigned to Group B. After treatment with sacubitril/valsartan plus dapagliflozin for a median follow-up period of 189 days (IQR, 180-276), significant improvements of cardiac function were achieved in Group A. Median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was significantly decreased from 2585 pg/ml (1014-3702.5) to 1260.5 pg/ml (439.8-2214.3) (P < 0.001). Mean left ventricular ejection fraction (LVEF) improved from 34.7 ± 4.6% to 39.2 ± 7.5% (P < 0.001). Mean daily dose of loop diuretics decreased from 37.1 ± 17.3 mg/day to 25.9 ± 18.5 mg/day (P < 0.001). Regarding safety, both systolic blood pressure (P = 0.002) and diastolic blood pressure (P = 0.002) significantly decreased. For patients in Group B, significant improvements in mean LVEF (P < 0.001), decreases in mean daily dose of loop diuretics (P = 0.001) and reductions in diastolic blood pressure (P = 0.023) were observed. Strikingly, both median Δ NT-proBNP (P = 0.04) and median Δ LAD (P = 0.006) in Group A were more pronounced in comparison with those seen in Group B. Conclusions: The combined use of sacubitril/valsartan and dapagliflozin was associated with improved cardiac function in patents with HFrEF, and led to greater reductions in LAD and NT-proBNP levels compared to sacubitril/valsartan monotherapy. These findings suggest that the combination therapy may offer more potent cardiovascular benefits.

Efficacy and safety of low-dose sacubitril/valsartan in heart failure patients: A systematic review and meta-analysis.

BACKGROUND: Controversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF). HYPOTHESIS: Low-dose sacubitril/valsartan might also be effective and safe in HF patients. METHODS: Electronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome. RESULTS: A total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan. CONCLUSIONS: Compared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.