Liang Yin

Effect of Statins in Preventing Postoperative Atrial Fibrillation Following Cardiac Surgery

BACKGROUND Postoperative occurrence of AF has been associated with less favourable outcomes in patients undergoing cardiac surgery and may result in increased postoperative morbidity and mortality. OBJECTIVES A focused clinical question was designed and a meta-analysis of published studies was performed to identify the effect of preoperative use of statins on the occurrence of AF after cardiac surgery. METHODS Using the Medline database, the Cochrane clinical trials database and online clinical trial databases, we reviewed all RCTs and observational studies examining the effect of statins on AF occurrence following cardiac surgery. We searched for the literature published before April 2009 and earlier. RESULTS This analysis identified six studies (observational studies) which examined the effect of preoperative use of statins on AF occurrence following cardiac surgery, involving 10,165 patients. Contradictory to most of previous studies, the overall outcomes suggested that the statins group did not have a significant decrease in AF occurrence following cardiac surgery comparing to control group (P=0.19). CONCLUSIONS The preoperative medication of statins showed no significant decrease in AF occurrence following cardiac surgery in this meta-analysis result. More prospective studies and researches are needed to explore and demonstrate the accurate mechanism and effect of statins on postoperative AF.

CHADS2 and CHA2DS2-VASc Scoring Systems for Predicting Atrial Fibrillation following Cardiac Valve Surgery

Objective Clinical use of CHADS2 and CHA2DS2-VASc scoring systems for predicting AF following cardiac surgery have been reported in previous studies and demonstrated well-validated predictive value. We sought to investigate whether the two scoring systems are effective for predicting new-onset of AF following cardiac valve surgery and to demonstrate its potential utility of clinical assessment. Methods Medical records of all patients underwent cardiac valve surgeries during the period of January 2003 and December 2013 without preoperative AF at the cardiac center of our university were reviewed. The main outcome end point of our study was the early new-onset of AF following cardiac valve surgery. Results There were overall 518 patients involved in this study, with 234 (45.17%) developed POAF following valve surgery. Patients with POAF had older age (P=0.23) and higher BMI (P=0.013) than those without POAF. History of heart failure (P=0.025), hypertension (P=0.021), previous stroke or TIA (P=0.032), coronary artery disease (P=0.001), carotid artery disease (P=0.024) and preoperative medication of statins (P=0.021) were significantly more recorded in POAF group. Patients with POAF also had higher LAD (P=0.013) and E/e’ ratio (P<0.001). The CHADS2 and CHA2DS2-VASc scores were significantly higher in patients with POAF (P=0.002; P<0.001), and under univariate and multivariate regression analysis the CHADS2 and CHA2DS2-VASc scores were significant predictors of POAF (P=0.001; P<0.001). Based on stratification of CHADS2 and CHA2DS2-VASc scores, the Kaplan-Meier analysis obtained a higher POAF rate on patients with higher stratification of CHADS2 and CHA2DS2-VASc scores (P<0.001; P<0.001). Conclusion In conclusion, CHADS2 and CHA2DS2-VASc scores were directly associated with the incidence of POAF following valve surgery and a higher score was strongly predictive of POAF.

Coronary artery bypass grafting versus combined coronary artery bypass grafting and mitral valve repair in treating ischaemic mitral regurgitation: a meta-analysis.

BACKGROUND Ischaemic mitral regurgitation (IMR) is commonly manifested after coronary artery disease, but it is still controversial as to whether coronary artery bypass grafting (CABG) alone improves postoperative outcome. OBJECTIVES A focussed clinical question was designed and a meta-analysis of published studies was performed to identify the impact of mitral valve repair (MVR) in patients with IMR undergoing CABG versus those undergoing CABG alone. METHODS Using the Medline database, the Cochrane clinical trials database and online clinical trial databases, we reviewed all RCTs and observational studies examining the impact of MVR and CABG in treating patients with IMR. We searched for literature published before September 2013 and earlier. RESULTS This analysis identified five studies which examined the impact of CABG alone versus combined CABG and MVR in treating patients with IMR, involving 1038 patients, with 423 patients undergoing CABG alone and 615 were performed combined CABG and MVR procedures. There was significant improvement in postoperative mitral regurgitation (MR) grade in combined group, comparing with CABG alone group (WMD: 1.34, 95% CI: 0.47 to 2.21, p = 0.003), but no significant differences were noted between the CABG plus MVR group and CABG alone group in terms of in-hospital mortality (OR: 0.84, 95% CI: 0.44 to 1.61, p = 0.60), MR grade improvement rate (OR: 0.19, 95% CI: 0.02 to 1.66, p = 0.13), postoperative mean NYHA functional class (WMD: 0.33, 95% CI: -0.29 to 0.94, p = 0.30) and five-year survival (OR: 0.77, 95% CI: 0.34 to 1.73, p = 0.53). CONCLUSIONS Compared with CABG alone, patients who underwent combined CABG and MVR procedures showed a greater improvement in postoperative MR grade, but in terms of in-hospital mortality, MR grade improvement rate, postoperative mean NYHA functional class and five-year survival, adding MVR to CABG surgery lacks evidence to show its superiority.

Surgical treatment of cardiac tumors: a 5-year experience from a single cardiac center

BACKGROUND Cardiac tumors are rare but manifested with various clinical presentations and often cause unexpected symptoms or sudden death. The objective is to review the clinical presentation, histopathological spectrum, mortality and follow-up data of patients with cardiac tumors following surgery treatment over a period of 5 years. METHODS We retrospectively collected the medical records of all patients diagnosed of cardiac tumors in the period between January 2008 and December 2013 at the cardiac center of our university. Clinical histories, perioperative data, surgical findings, efficacy and follow-up data were reviewed in our study. Patients were divided into two groups according to site distribution of the tumors in the heart. RESULTS A total of 131 patients underwent surgical treatment of cardiac tumors were enrolled in this study, with a mean age of 51.39±16.37. The result of analysis showed that 79.47% (n=104) of the primary intracardiac tumors were benign, while primary malignant neoplasms accounted for 16.03% (n=21) of all patients, with the remainder (n=6, 4.6%) metastatic tumors transferred from other organs. Among all patients there were 2 in-hospital deaths and the survival rate in all patients at 1-year, 3-year and 5-year follow up was 83.20%, 78.62% and 66.41% respectively. Both patients with tumors in the left and right heart had similar basic characteristics except sex gender (P=0.002), BSA (P=0.045) and weight (P=0.033). Compared with patients with tumors in the right heart, patients with tumors in the left heart had significant higher CPB time (P<0.001), cross clamp time (P<0.001) and time of mechanical ventilation (P<0.001), and they also had longer ICU stay (P<0.001) but not total hospital stay (P=0.434). CONCLUSIONS Surgical resection represents an effective protocol in treating cardiac tumors. Data in our study of cardiac tumors on frequency and allocation were consistent with previous reports which may provide useful clinical evidence on shared data, and data revealed that patients with malignant cardiac tumors had significant lower survival both in hospital and long-term follow-up.

Human Epicardial Adipose Tissue cTGF Expression is an Independent Risk Factor for Atrial Fibrillation and Highly Associated with Atrial Fibrosis

Epicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0.001). Galectin-3 expression was significantly higher in EAT than in SAT or PAT (P < 0.001), with no significant differences between patients with AF and SR (P > 0.05). Leptin and vaspin expression were lower in EAT than in PAT (P < 0.001). Trichrome staining showed that the fibrosis was much more severe in patients with AF than SR (P < 0.001). We found a linear relationship between cTGF mRNA expression level and collagen volume fraction (y = 1.471x + 27.330, P < 0.001), and logistic regression showed that cTGF level was an independent risk factor for AF (OR 2.369, P = 0.027). In conclusion, highly expressed in EAT, cTGF is associated with atrial fibrosis, and can be an important risk factor for AF.

Usefulness of CHA 2 DS 2 -VASc Scoring Systems for Predicting Risk of Perioperative Embolism in Patients of Cardiac Myxomas Underwent Surgical Treatment

Cardiac myxomas are rare but manifested with risk of embolism and often cause unexpected symptoms or sudden death. We retrospectively collected the medical records of patients diagnosed of cardiac myxomas at the cardiac center of our university. Overall 465 patients were included in this study, patients in the embolism group had significantly higher CHA2DS2-VASc scores (P = 0.005). In embolic group, stroke was recorded in 110 (77.14%) patients, while embolic events in the limbs were observed in 10 (2.15%) and 9(1.93%) developed splenic infarction. Patients in embolism group had older age (P = 0.021) and higher BMI (P  <0.001) than those in non-embolism group. There was no significant difference between two groups in terms of time of mechanical ventilation (P = 0.065), ICU stay (P = 0.053), hospital stay (P = 0.071) and volume of drainage (P = 0.083), blood transfusions (P = 0.060) except that patients with embolic events had significantly higher incidence of postoperative atrial fibrillation (P = 0.032) and lower survival rate (P < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of embolism in patients with cardiac myxomas (P = 0.015; P = 0.003) and the Kaplan-Meier analysis obtained a higher rate of embolism in patients with higher stratification of CHA2DS2-VASc scores (P = 0.002). In conclusion, CHA2DS2-VASc scoring scheme was strongly predictive of stroke and embolic events in patients with cardiac myxomas.

YKL-40 is highly expressed in the epicardial adipose tissue of patients with atrial fibrillation and associated with atrial fibrosis

BackgroundYKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well as cardiovascular diseases. We investigated the association between YKL-40 expression in epicardial adipose tissue (EAT) and atrial fibrosis in patients with atrial fibrillation (AF).MethodsBlood samples, subcutaneous adipose tissue (SAT), paracardial adipose tissue (PAT), EAT, and adjacent atrial myocardium were acquired from patients receiving coronary artery bypass grafts. The patients were divided into the AF group (n = 28) and the sinus rhythm (SR) group (n = 36).ResultsWe did not detect a significant difference in the serum YKL-40 levels in the SR and AF groups (P = 0.145). Quantitative real-time PCR showed that YKL-40 (CHI3L1) mRNA levels in the EAT were significantly higher than in the SAT or PAT of AF patients, or the EAT of SR patients (All P < 0.001). We found similar results for YKL-40 protein levels by immunohistochemistry. Masson staining showed significantly more fibrosis in AF patients than in SR patients (P < 0.001). Western blotting indicated that AF patients had significantly higher expression of collagen I (P = 0.039). We found a linear relationship between YKL-40 mRNA expression and the collagen volume fraction of the atrial myocardium (y = 3.576x + 26.205, P < 0.001). Multivariate linear regression analysis revealed that body mass index is an independent risk factor for YKL-40 expression in EAT (β = 0.328, P = 0.011).ConclusionsYKL-40, which is highly expressed in the EAT of patients with AF, is affected by body mass index and associated with atrial fibrosis, which may contribute to the development of AF.

Smoking as a Risk Factor for the Occurrence of Atrial Fibrillation in Men Versus Women: A Meta-Analysis of Prospective Cohort Studies

BACKGROUND Although smoking is known to be associated with cardiovascular diseases, the number of large-scale cohort studies on the association between smoking and atrial fibrillation (AF) is limited and the results obtained are also inconsistent, and even fewer studies have addressed the difference between the male and female genders. The present study was intended to clarify and quantify the association between smoking and the risk of AF in men versus women. METHODS Using AF- and smoking-related keywords, a comprehensive literature search on PubMed, Embase and Web of Science was conducted with a time limit until December 2016, which was followed by manual screening, quality assessment and data extraction. The pooled relative risk (RR) of the included studies was estimated by using the random-effects model. Subgroup, heterogeneity and sensitivity analyses were also conducted. RESULTS A total of 14 prospective studies and 222,159 individuals were included in this meta-analysis, and the pooled RR of the 14 studies was 1.24 (95% CI, 1.12-1.36; p<0.0001) for the occurrence of AF in smoking populations. The pooled RR in men was 1.38 (95% CI, 1.21-1.57 p<0.0001) versus 1.28 in women (95% CI, 0.93-1.76; p=0.1356). The male-to-female ratio of relative risk (RRR) was 1.17 (95% CI, 0.84-1.63; p=0.3418) of smoking versus non-smoking individuals. CONCLUSION Smoking is a risk factor for the occurrence of AF. Compared with women, male smokers are more likely to develop AF.

Activation of TGF-β1/α-SMA/Col I Profibrotic Pathway in Fibroblasts by Galectin-3 Contributes to Atrial Fibrosis in Experimental Models and Patients

Background/Aims: This study aimed to evaluate whether galectin-3 (Gal-3) contributes actively to atrial fibrosis both in patients and experimental atrial fibrillation (AF) models. Methods: Mouse HL-1 cardiomyocytes were subjected to rapid electrical stimulation (RES) to explore Gal-3 expression and secretion levels by western blotting (WB) and enzyme linked immunosorbent assay (ELISA). Neonatal rat cardiac fibroblasts were treated with conditioned culture medium and recombinant human Gal-3 to evaluate the activation of the transforming growth factor (TGF)-β1/α-smooth muscle actin (SMA)/collagen I (Col I) profibrotic pathway (WB) and fibroblast proliferation with a Cell Counting Kit-8 (CCK-8). Furthermore, in the rapid atrial pacing (RAP) rabbit AF model, atrial Gal-3 expression and its effects on the profibrotic pathway were evaluated (WB and Masson’s trichrome staining). Moreover, 44 consecutive patients who underwent single mitral valve repair/replacement were included, consisting of 28 patients with persistent AF (PeAF) and 16 with sinus rhythm (SR). Coronary sinus blood was also sampled to test circulating Gal-3 levels (ELISA), and atrial myocardium Gal-3 and its downstream TGF-β1/α-SMA pathway were also measured by WB and immunohistochemical staining. Results: Gal-3 expression in HL-1 cells and its secretion level in culture medium were greatly increased after 24 h RES. Treatment of neonatal rat cardiac fibroblasts with conditioned media collected from the RES group or recombinant human Gal-3 protein (10 and 30 µg/mL) for 72 h induced the activation of the TGF-β1/α-SMA/Col I profibrotic pathway. RAP increased Gal-3 levels and activated the TGF-β1/α-SMA/Col I pathway in rabbit left atria, while the Gal-3 inhibitor N-acetyllactosamine, injected at 4.5 mg/kg every 3 days, mitigated these adverse changes. Furthermore, Gal-3 levels in coronary sinus blood samples and myocardial Gal-3 expression levels were higher in the PeAF patients than in the SR patients, and higher level profibrotic pathway activation was also confirmed. Conclusions: Activation of Gal-3 expression in the atria can subsequently activate the TGF-β1/α-SMA/Col I pathway in cardiac fibroblasts, which may enhance atrial fibrosis.

Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

Background/Aims: Caffeic acid (CA) is known to possess multiple biological activities including anti-cancer activities. However, the molecular mechanisms underlying these activities in non-small-cell lung cancer (NSCLC) cells are not fully understood. We attempted to clarify whether CA could enhance paclitaxel (PTX)-induced cytotoxicity in H1299 cells. Methods: First, we tested the cytotoxic effects in both H1299 cells and normal human Bease-2b cells by cell proliferation experiments. Next, we use Annexin V/propidium iodide apoptosis analysis and flow cytometric analysis to investigate apoptosis and cell cycle arrest under the treatments mentioned above. To further pinpoint changes in apoptosis, we tested the caspase-associated apoptotic pathway, which involves the activities of caspase-3 and caspase-9. Moreover, apoptosis-related proteins and MAPK pathway proteins were examined by western blot. An H1299 xenograft nude mice model was used to further evaluate the tumor-suppressing effects of CA and PTX in vivo. Results: Combination treatment with low-dose CA and PTX decreased the proliferation of NSCLC H1299 cells but not normal Beas-2b cells. Flow cytometry showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. Caspase-3 and caspase-9 activities were both increased after CA treatment. Furthermore, CA increased the PTX-induced activation of Bax, Bid, and downstream cleaved PARP, and phosphorylation of extracellular signal regulated kinase1/2 and c-Jun NH2-terminal protein kinase1/2. An in vivo tumor-suppression assay demonstrated that CA and PTX combined treatment exerted a more effective suppressive effect on tumor growth in H1299 xenografts without causing significant adverse effects. Conclusions: Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.