Background: Epicardial adipose tissue (EAT) accumulation is associated with multiple cardiometabolic risk factors and prognosis of heart failure with preserved ejection fraction (HFpEF). The correlation between EAT density and cardiometabolic risk and the effect of EAT density on clinical outcome in HFpEF remain unclear. We evaluated the relationship between EAT density and cardiometabolic risk factors, also the prognostic value of EAT density in patients with HFpEF. Methods: We included 154 HFpEF patients who underwent noncontrast cardiac computed tomography (CT) and all patients received follow-up. EAT density and volume were quantified semi-automatically. The associations of EAT density and volume with cardiometabolic risk factors, metabolic syndrome and the prognostic impact of EAT density were analyzed. Results: Lower EAT density was associated with adverse changes in cardiometabolic risk factors. Each 1 HU increase in fat density, BMI was 0.14 kg/m² lower (95% CI 0.08–0.21), waist circumference was 0.34 cm lower (95% CI 0.12–0.55), non-HDL-cholesterol was 0.02 mmol/L lower (95% CI 0–0.04), triglyceride was 0.03 mmol/L lower (95% CI 0.01–0.04), fasting plasma glucose was 0.05 mmol/L lower (95% CI 0.02–0.08), TyG index was 0.03 lower (95% CI 0.02–0.04), Log₂(TG/HDL-C) was 0.03 lower (95% CI 0.02–0.05), METS-IR was 0.36 lower (95% CI 0.23–0.49), MetS Z-score was 0.04 lower (95% CI 0.02–0.06), and Log₂(CACS + 1) was 0.09 lower (95% CI 0.02–0.15). After adjusting for BMI and EAT volume, the associations of non-HDL-cholesterol, triglyceride, fasting plasma glucose, insulin resistance indexes, MetS Z-score, and CACS with fat density remained significant. The area under the curve (AUC) for the presence and severity of metabolic syndrome was greater in EAT density than volume (AUC: 0.731 vs 0.694, 0.735 vs 0.662, respectively). Over a median follow-up of 16 months, the cumulative incidence of heart failure readmission and composite endpoint increased with lower level of EAT density (both p < 0.05). Conclusions: EAT density was an independent impact factor of cardiometabolic risk in HFpEF. EAT density might have better predictive value than EAT volume for metabolic syndrome and it might have prognostic value in patients with HFpEF.

Cardiac fibrosis is the most important pathogenesis leading to cardiac remodeling and heart failure after myocardial infarction (MI). Tissue nonspecific alkaline phosphatase (TNAP) has recently been recognized as a potential prognostic factor for MI. Nevertheless, the role of TNAP in cardiac fibrosis after MI has not been explicitly delineated. A systematic review and meta-analysis was conducted to assess the effect of serum TNAP levels on mortality in patients with ischemic heart disease (IHD). A correlation analysis was performed to investigate the relationship between serum levels of TNAP and biomarkers of fibrosis. Heart biopsies from patients with MI and a mouse model of MI were used to detect the expression and distribution of TNAP. Furthermore, we established adenovirus-mediated knockdown and overexpression of TNAP, using a combination of in vivo and in vitro studies in mice, to determine the role and mechanism of TNAP in cardiac fibrosis after MI. In the in vitro studies, cardiac fibroblasts were cultured on soft plates. After searching the main databases and performing a detailed assessment of the full-text articles, eight studies with 14,816 individuals were included in the quantitative analysis. We found that a high serum TNAP level was associated with an increased risk of mortality in patients with IHD and MI. The correlation analysis revealed a positive correlation between serum TNAP levels and the concentration of fibrosis biomarkers (PICP/PIIINP). The expression of TNAP was upregulated in the myocardium of patients with MI and in a mouse model of MI, accompanied by fibroblast activation and the deposition of collagen fibers. In the in vivo study, TNAP knockdown ameliorated cardiac fibrosis and improved cardiac function in mice. TNAP overexpression aggravated cardiac fibrosis and worsened cardiac function. In the in vitro study, TNAP promoted cardiac fibroblast differentiation, migration and proliferation. Mechanistically, the pro-fibrotic effect of TNAP on cardiac fibroblasts was at least partially achieved by activating the TGF-β1/Smads and ERK1/2 signaling pathways. Based on these findings, TNAP plays an important pro-fibrotic role in cardiac fibrosis after MI by activating TGF-β/Smads and ERK1/2 signaling, indicating that it functions as a potential regulator of and therapeutic target in cardiac fibrosis. This work was supported by the National Natural Science Foundation of China.

Background: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients.Methods: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death.Results: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4⁺T cell level were older and more often male compared to those with higher CD4⁺T cell level. Reduced CD8⁺T cell level was an indicator of the severity of COVID-19. Both decreased CD4⁺T [HR:13.659; 95%CI: 3.235–57.671] and CD8⁺T [HR: 10.883; 95%CI: 3.277–36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4⁺T cell level was an independent predictor of in-hospital death in COVID-19 patients.Conclusions: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8⁺T cell level, not the CD4⁺T cell level, that reflected the severity of the patient’s disease. Only reduced CD4⁺T cell level was independently associated with increased in-hospital death in COVID-19 patients.Trial registration: Prognostic Factors of Patients With COVID-19,NCT04292964. Registered 03 March 2020. Retrospectively registered.

Aims: This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. Methods and results: PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53–2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25–1.66), cardiac death (RR: 1.56, 95% CI: 1.32–1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37–3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05–1.25). Conclusions: Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.