The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
It has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A (VEGFA) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are currently unclear. Here, this study was designed to determine the relationship between long non-coding RNA (lncRNA) H19, mircoRNA29b (miR-29b), and VEGFA in the development of diabetes mellitus (DM). We demonstrate that H19 is upregulated and miR-29b downregulated in individuals with DM and directly binds miR-29b. VEGFA is the target of miR-29b in the vascular endothelium of individuals with DM. We found that positive modulation of miR29b and inhibition of H19 and VEGFA significantly attenuates high glucose-induced endothelial inflammation and oxidative stress. We also found that the protein kinase B/endothelial nitric oxide synthase (AKT/eNOS) signal pathway in endothelial cells is activated through regulation of miR29b and H19 endogenous RNAs. We conclude that H19 suppression protects the endothelium against high glucose-induced inflammation and oxidative stress in endothelial cells by upregulation of miR-29b and downregulation of VEGFA through AKT/eNOS signal pathway activation. These results suggest a novel link between dysregulated ncRNA expression, inflammation, and the signaling pathway in the vascular endothelium of individuals with DM, indicating a promising strategy for preventing cardiovascular disease in such individuals.
In this paper, three-dimensional holey graphene (3D-HG) was used to fabricate a sensitive electrochemical sensing platform. Threedimensional holey graphene with a 3D porous network and in-plane nanopores possesses a large surface area and more exposed edge planes, contributing to a remarkable increase of electrochemically active sites and of electron-transfer rate. As a result, the excellent electrocatalytic activities of 3D-HG modified electrode toward ascorbic acid (AA), uric acid (UA), and nitrite oxidation were observed. This sensor showed excellent properties for AA, UA and nitrite detection using differential pulse voltammograms, including low detection limits, wide linear ranges and high sensitivities. Moreover, the applicability of 3D-HG modified electrode was tested in real samples with the good accuracy and satisfying recovery.
BackgroundEmergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) helps to reduce the occurrence of major adverse cardiovascular events (MACEs) such as death, cardiogenic shock, and malignant arrhythmia, but in-hospital MACEs may still occur after emergency PCI, and their mortality is significantly increased once they occur. The aim of this study was to investigate the risk factors associated with MACE during hospitalization after PCI in STEMI patients, construct a nomogram prediction model and evaluate its effectiveness.MethodsA retrospective analysis of 466 STEMI patients admitted to our hospital from January 2018 to June 2022. According to the occurrence of MACE during hospitalization, they were divided into MACE group (n = 127) and non-MACE group (n = 339), and the clinical data of the two groups were compared; least absolute shrinkage and selection operator (LASSO) regression was used to screen out the predictors with non-zero coefficients, and multivariate Logistic regression was used to analyze STEMI Independent risk factors for in-hospital MACE in patients after emergency PCI; a nomogram model for predicting the risk of in-hospital MACE in STEMI patients after PCI was constructed based on predictive factors, and the C-index was used to evaluate the predictive performance of the prediction model; the Bootstrap method was used to repeat sampling 1,000 Internal validation was carried out for the second time, the Hosmer-Lemeshow test was used to evaluate the model fit, and the calibration curve was drawn to evaluate the calibration degree of the model. Receiver operating characteristic (ROC) curves were drawn to evaluate the efficacy of the nomogram model and thrombolysis in myocardial infarction (TIMI) score in predicting in-hospital MACE in STEMI patients after acute PCI.ResultsThe results of LASSO regression showed that systolic blood pressure, diastolic blood pressure, Killip grade II-IV, urea nitrogen and left ventricular ejection fraction (LVEF), IABP, NT-ProBNP were important predictors with non-zero coefficients, and multivariate logistic regression analysis was performed to analyze that Killip grade II-IV, urea nitrogen, LVEF, and NT-ProBNP were independent factors for in-hospital MACE after PCI in STEMI patients; a nomogram model for predicting the risk of in-hospital MACE after PCI in STEMI patients was constructed with the above independent predictors, with a C-index of 0.826 (95% CI: 0.785–0.868) having a good predictive power; the results of H-L goodness of fit test showed χ2 = 1.3328, P = 0.25, the model calibration curve was close to the ideal model, and the internal validation C-index was 0.818; clinical decision analysis also showed that the nomogram model had a good clinical efficacy, especially when the threshold probability was 0.1–0.99, the nomogram model could bring clinical net benefits to patients. The nomogram model predicted a greater AUC (0.826) than the TIMI score (0.696) for in-hospital MACE after PCI in STEMI patients.ConclusionUrea nitrogen, Killip class II-IV, LVEF, and NT-ProBNP are independent factors for in-hospital MACE after PCI in STEMI patients, and nomogram models constructed based on the above factors have high predictive efficacy and feasibility.
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