The association between the MELD-XI score and heart failure in patients with acute myocardial infarction after coronary artery stenting-a retrospective study.

Background: The model for end-stage liver disease (MELD) score is a marker used to evaluate end-stage liver disease in patients with liver failure and is suggested to be valuable in evaluating heart diseases such as heart failure. Because patients with heart failure and myocardial infarction often use anticoagulants, there is an impact on the international normalized ratio (INR). Therefore, removing the INR from MELD score to form MELD-XI score may help to more accurately evaluate the cardiac function in patients with heart failure. This study was conducted to examine the predictive value of MELD-XI score in patients with acute myocardial infarction after coronary artery stenting, as there is a lack of literature in this area. Methods: The data of 318 patients with acute myocardial infarction admitted to The People's Hospital of Dazu from January 2018 to January 2021 was retrospectively collected. According to the MELD-XI score on admission, the patients were divided into a high-MELD-XI score group (n=159) and a low-MELD-XI score group (n=159). The patients were followed up for 1 year after surgery to observe the long-term prognosis and the long-term prognosis of the 2 groups was compared. Results: Compared with that in the low-MELD-XI score group, the left ventricular ejection fraction in the high-MELD-XI score group was significantly reduced (51.61%±7.66% vs. 60.48%±5.94%; P<0.001), while the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased significantly (821.58±461.81 vs. 723.51±335.16 ng; P=0.031). The MELD-XI score had a certain predictive value for heart failure in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.730 (95% CI: 0.670-0.791; P<0.001). The MELD-XI score had a predictive value for death in patients with acute myocardial infarction after coronary artery stenting, and the area under the curve was 0.704 (95% CI: 0.564-0.843; P=0.022). MELD-XI score was significantly negatively correlated with left ventricular ejection fraction in patients with acute myocardial infarction after coronary artery stenting (r=-0.444; P<0.001). Conclusions: MELD-XI could evaluate the cardiac function of patients with acute myocardial infarction after coronary artery stenting, which was valuable in predicting the prognosis.

Cardiac-specific deletion of FDPS induces cardiac remodeling and dysfunction by enhancing the activity of small GTP-binding proteins.

The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps-/- mice) to investigate the role of FDPS in cardiac homeostasis. Cardiac function was assessed using echocardiography. Left ventricles were examined and tested for histological and molecular markers of cardiac remodeling. Our results showed that FDPS levels were downregulated in samples from patients with cardiomyopathy. Furthermore, c-Fdps-/- mice exhibited cardiac remodeling and dysfunction. This dysfunction was associated with abnormal activation of Ras and Rheb, which may be due to the accumulation of geranyl pyrophosphate. Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways. Moreover, administration of farnesyltransferase inhibitors attenuated cardiac remodeling and dysfunction in c-Fdps-/- mice. These results indicate that FDPS plays an important role in cardiac homeostasis. Deletion of FDPS stimulates the downstream mTOR and ERK signaling pathways, resulting in cardiac remodeling and dysfunction. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Inhibition of miR-1224 suppresses hypoxia/reoxygenation-induced oxidative stress and apoptosis in cardiomyocytes through targeting GPX4.

We have focused on the underlying role of miR-1224 in cardiomyocyte injury stimulated by hypoxia/reoxygenation (H/R). In the current study, the rat cardiomyocyte cell line H9C2 was used to construct a H/R cell model to validate the cardioprotective effects of miR-1224. Data from the dual-luciferase assay revealed that the glutathione peroxidase 4 (GPX4) was a direct target of miR-1224. Expression of miR-1224, determined using qRT-PCR, was remarkably increased while that of GPX4 protein, evaluated via western blotting, was significantly decreased in cardiomyocytes in response to H/R exposure. ROS generation, superoxide dismutase (SOD) activity, concentrations of malondialdehyde (MDA) and 4-hydroxy aldehydes (4-HNE), and H9C2 cell apoptosis were further evaluated following overexpression of miR-1224 or silencing of GPX4 in H9C2 cells. H9C2 cells under H/R conditions displayed increased synthesis of ROS, along with overexpression of miR-1224 and downregulation of GPX4. SOD activity was significantly decreased while concentrations of MDA and 4-HNE were markedly increased under H/R injury conditions. In addition, miR-1224 mimic or GPX4 siRNA plasmids dramatically enhanced H/R-mediated apoptosis, Bax expression and caspase-3 activity, with a concomitant reduction in Bcl-2 expression. Conversely, inhibition of miR-1224 exerted suppressive effects on oxidative stress and apoptosis in H9C2 cells under H/R conditions. Interestingly, silencing of GPX4 attenuated the negative effects of miR-1224 inhibition. Our results suggested that inhibition of miR-1224 caused resistance to H/R and diminished oxidative stress in vitro through targeting of GPX4.

Higher Plasma Pentraxin-3 Level Predicts Adverse Clinical Outcomes in Patients With Coronary Artery Disease: A Meta-Analysis of Cohort Studies.

Background: Association between plasma pentraxin-3 (PTX-3) and clinical outcomes in patients with coronary artery disease (CAD) remains not fully determined. An updated meta-analysis of cohort studies was performed to systematically evaluate the association. Methods: Cohort studies evaluating the association between plasma PTX-3 and adverse outcomes [mortality and major adverse cardiovascular events (MACEs)] in adults with CAD were identified by systematic search of PubMed, Embase, and Web of Science databases. Only studies with multivariate analysis were included. A random-effects model incorporating the potential intrastudy heterogeneity was used for the meta-analysis. Results: A total of 16 studies including 11,007 patients were included. Pooled results showed that patients with highest level of PTX-3 were independently associated with higher risk of mortality [adjusted risk ratio (RR): 2.09, 95% CI: 1.60 to 2.74, p < 0.001; I 2 = 50%] and MACEs (adjusted RR: 1.80, 95% CI: 1.43 to 2.28, p < 0.001; I 2 = 49%). Subgroup analyses showed that the associations between PTX-3 and poor prognosis in CAD were consistent in patients with ST-segment elevation myocardial infraction, non-ST-segment elevation acute coronary syndrome, and stable CAD (p < 0.05 for each subgroup). Besides, the association between PTX-3 and increased incidence of mortality and MACEs were consistent in short-term (within 1 year) and long-term (over 1 year) studies and in studies with or without adjustment of C-reactive protein (CRP) (p < 0.05 for each subgroup). Conclusion: Higher plasma PTX-3 is associated with poor prognosis in patients with CAD, which may be independent of the CAD subtype, follow-up durations, and adjustment of CRP.