Serum human epididymis protein 4 levels in the prediction of the recurrence of atrial fibrillation after catheter ablation.

The aim of this study is to assess serum human epididymis protein 4 (HE-4) levels as a biomarker for predicting the recurrence of atrial fibrillation (AF) after catheter ablation. This was a prospective observational study that enrolled one hundred eighty-four consecutive nonvalvular AF patients (65 persistent, 119 paroxysmal) who were eligible for their first ablation. Multiple Cox proportional hazards models and Kaplan-Meier curve analyses were used to test the association between serum HE-4 levels and AF recurrence after catheter ablation. During the 12-month follow-up, we observed that 47 patients (25.5%) experienced AF recurrence. Patients were divided into tertiles of HE-4 level (T1: < 50 pmol/L; T2: ≥ 50 pmol/L). The AF recurrence rate of higher serum HE-4 level patients was significantly increased (34.6% vs 13.8%, P < 0.001). Generalized additive models were used to visually assess functional relationships between the serum HE-4 levels and the risk of AF recurrence. When stratified with serum levels as the cut-off value, Kaplan-Meier analysis showed that patients with serum HE-4 levels (> 50 pmol/L) had a significantly increased risk of AF recurrence. In addition, multivariate Cox proportional hazard modelling revealed that HE-4 (≥ 50 pmol/L) (HR 2.65; 95% CI 1.34, 5.27, P = 0.005) was independent predictors of AF recurrence. Serum HE-4 levels in patients with AF are associated with postoperative recurrence of AF, and high HE-4 levels are an independent predictor of AF recurrence after ablation.

Use of the cardiopulmonary coupling index based on refined composite multiscale entropy for prognostication of acute type A aortic dissection.

Objectives: The aim of this study is to assess the influence of cardiopulmonary coupling (CPC) based on RCMSE on the prediction of complications and death in patients with acute type A aortic dissection (ATAAD). Background: The cardiopulmonary system may be nonlinearly regulated, and its coupling relationship with postoperative risk stratification in ATAAD patients has not been studied. Methods: This study was a single-center, prospective cohort study (ChiCTR1800018319). We enrolled 39 patients with ATAAD. The outcomes were in-hospital complications and all-cause readmission or death at 2 years. Results: Of the 39 participants, 16 (41.0%) developed complications in the hospital, and 15 (38.5%) died or were readmitted to the hospital during the two-year follow-up. When CPC-RCMSE was used to predict in-hospital complications in ATAAD patients, the AUC was 0.853 (p < 0.001). When CPC-RCMSE was used to predict all-cause readmission or death at 2 years, the AUC was 0.731 (p < 0.05). After adjusting for age, sex, ventilator support (days), and special care time (days), CPC-RCMSE remained an independent predictor of in-hospital complications in patients with ATAAD [adjusted OR: 0.8 (95% CI, 0.68-0.94)]. Conclusion: CPC-RCMSE was an independent predictor of in-hospital complications and all-cause readmission or death in patients with ATAAD.

Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention.

1. Inflammation is central to the pathogenesis of acute coronary syndrome (ACS) and is associated with adverse clinical outcomes after percutaneous coronary intervention (PCI). Recent in vitro work has demonstrated the anti-inflammatory effect of berberine, a primary component of the traditional Chinese medicine 'umbellatine'. In the present study, we further tested whether berberine had any beneficial effects on ACS patients following PCI. 2.In all, 130 ACS patients undergoing PCI were recruited to the present study. Sixty-one patients were treated with berberine (300 mg, t.i.d., for 30 days) in addition to standard therapy, whereas the remaining patients received standard therapy alone. Circulating inflammatory markers were measured by ELISA, whereas serum lipid profiles were measured by routine chemical assays. 3.In the berberine-treated group, matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, C-reactive protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly reduced relative to baseline values. Furthermore, the changes in MMP-9, ICAM-1 and VCAM-1 from baseline to after 1 month of treatment differed significantly between the two patient groups. There was a tendency for berberine to induce a slightly greater reduction in low-density lipoprotein cholesterol and triglycerides than standard therapy alone, without affecting high-density lipoprotein cholesterol, but the differences failed to reach statistical significance. No severe adverse effects of berberine were observed. 4.The results of the present study provide the first clinical evidence of the anti-inflammatory action of berberine in ACS patients following PCI. Berberine may become adjunct therapy to further improve clinical outcomes via its anti-inflammatory effect in ACS patients.

[Relationship between antithrombin-III value with acute coronary syndrome and preprocedural TIMI flow grade].

OBJECTIVE: To explore the differences of antiprothrombin-III (AT-III) value in patients with acute coronary syndrome (ACS) and stable angina pectoris (SAP) and examine the association of AT-III value with preprocedural thrombolysis in myocardial infarction (TIMI) flow in ACS patients. METHODS: This study prospectively included 121 hospitalized ACS patients between February 2011 to June 2011, including ST-segment elevation myocardial infarction (STEMI, n = 50), non-ST segment elevation myocardial infarction (NSTEMI, n = 32) and unstable angina (UAP, n = 39). Meanwhile, 50 SAP cases during the same period were selected as the control group. The AT-III levels were measured by chromogenic substrate method before coronary angiography for all patients. RESULTS: (1) The AT-III levels were significantly lower in the ACS patients than those in the SAP cases. (2) In the STEMI subgroup, the AT-III levels were markedly lower in the patients with preprocedural TIMI flow grade ≤ 2 versus those with preprocedural TIMI flow grade 3 (86% ± 11% vs 93% ± 9%, P < 0.05). (3) In the USTEMI/UAP subgroup, the mean levels of AT-III were obviously lower in the patients with preprocedural TIMI flow grade ≤ 2 than those with preprocedural TIMI flow grade 3 (85% ± 8% vs 95% ± 8%, P < 0.01) and were notably lower in the patients with the culprit lesion stenosis ≥ 70% versus those with stenosis < 70% (88% ± 9% vs 94% ± 9%, P < 0.01). (4) Multivariable analysis identified AT-III value as an independent predictor of impaired preprocedural TIMI flow grade of culprit coronary artery in ACS patients. CONCLUSION: The AT-III levels were significantly lower in the ACS patients than those in the SAP patients. The activity of AT-III is positively correlated with the TIMI flow grade in ACS patients. In contrast, the activity of AT-III is negatively correlated with the severity of culprit vessel stenosis in the patients with NSTEMI. Thus AT-III level may be used to distinguish high-risk populations in ACS patients at an early stage.

Artemisinin inhibits extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 expression via a protein kinase Cδ/p38/extracellular signal-regulated kinase pathway in phorbol myristate acetate-induced THP-1 macrophages.

1. Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) by monocytes/macrophages has been proposed to play a significant role in atherosclerotic plaque progression and rupture. The aim of the present study was to explore whether artemisinin, a natural extract from Artemisia annua, could decrease EMMPRIN and MMP-9 expression in phorbol myristate acetate (PMA)-induced macrophages by regulating the protein kinase (PK) Cδ/c-Jun N-terminal kinase (JNK)/p38/extracellular signal-regulated kinase (ERK) pathway. 2. Human monocytic THP-1 cells were pretreated with 20-80 µg/mL artemisinin for 4 h or 1-10 µmol/L rottlerin for 1 h prior to stimulation with PMA (100 nmol/L) for another 48 h. Cells were collected to analyse the induction of EMMPRIN and MMP-9. Upstream pathway analysis using the PKCδ inhibitor rottlerin detected activation of the PKCδ/JNK/p38/ERK pathway. 3. Artemisinin (20-80 µg/mL) significantly inhibited the induction of EMMPRIN and MMP-9 at both the transcriptional and translational levels in a dose-dependent manner in PMA-induced macrophages. In addition, artemisinin (20-80 µg/mL) strongly blocked PKCδ/JNK/p38/ERK MAPK phosphorylation. The PKCδ inhibitor rottlerin (1-10 µmol/L) also significantly inhibited JNK/p38/ERK phosphorylation and decreased EMMPRIN and MMP-9 mRNA and protein expression. 4. The results of the present study suggest that artemisinin inhibits EMMPRIN and MMP-9 expression and activity by suppressing the PKCδ/ERK/p38 cascade in PMA-induced macrophages.

Assessment of High-Power Catheter Ablation in Patients With Atrial Fibrillation: A Meta-Analysis.

Background: High-power radiofrequency (RF) catheter ablation was considered as a promising alternative strategy to conventional-power ablation in the treatment of patients with atrial fibrillation (AF). This study sought to compare the efficacy and safety of high-power energy delivery to that of conventional-power setting in AF catheter ablation. Methods: We performed a systematic review of relevant literature in Pubmed, Embase, Cochrane library, and Google Scholar database. Sixteen eligible studies totaling 3,307 patients (1,929 for high-power ablation; 1,378 for conventional-power ablation) met inclusion criteria. Results: During a median 12 month follow-up, high-power ablation showed a significantly higher AF/atrial tachycardia-free survival rate in comparison with conventional-power ablation (risk ratio [RR] 1.09, 95% CI 1.02 to 1.15, p = 0.008). Notably, a high-power strategy convincingly decreased the procedure time (weighted mean difference [WMD] -46.11 min, 95% CI -59.15 to -33.07, p < 0.001) and RF ablation time (WMD -19.19 min, 95% CI -24.47 to -13.90, p < 0.001), along with reduced fluoroscopy time (WMD -7.82 min, 95% CI -15.13 to -0.68, p = 0.036). In addition, there was no perceptible difference in the potential risk of procedure-related complications between these two approaches (RR 0.81, 95% CI 0.48 to 1.37, p = 0.428). Conclusions: High-power RF catheter ablation was associated with an improvement in long-term sinus rhythm maintenance for treatment of AF, without exacerbating the risk of adverse events during the procedure. Impressively, high-power pulmonary vein isolation had the potential to shorten the application duration and minimize fluoroscopic exposure.

Elevated circulating level of P2X7 receptor is related to severity of coronary artery stenosis and prognosis of acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a severely life-threatening cardiovascular disease. Previous research has identified an association between the P2X7 receptor (P2X7R) and the development of atherosclerosis. However, the correlation of its expression with the clinical prognosis of patients with AMI remains unclear. The present study aimed to investigate the potential role of P2X7R in Chinese patients with AMI. METHODS: Seventy-nine patients with AMI and 48 controls were consecutively enrolled in this prospective observational study. Circulating P2X7R mRNA expression levels and other clinical variables were determined upon admission to the hospital. Patients were followed up for 360 days, and the end-point was considered as the occurrence of major adverse cardiovascular events (MACE). RESULTS: Circulating P2X7R mRNA expression level in peripheral blood mononuclear cells of patients with AMI were significantly higher than those in controls and had promising diagnostic ability of AMI with an area under the curve of 0.928. Furthermore, P2X7R was demonstrated to be correlated positively with the severity of coronary artery stenosis. Additionally, this is the first study to indicate that higher P2X7R mRNA expression is associated with a higher rate of MACE within 360 days after AMI. CONCLUSIONS: The present study showed that the circulating level of P2X7R was elevated in AMI patients and was closely associated with the severity of coronary artery stenosis and prognosis of AMI.

Melatonin against Myocardial Ischemia-Reperfusion Injury: A Meta-analysis and Mechanism Insight from Animal Studies.

AIMS: Myocardial reperfusion damage after severe ischemia was an important issue during a clinical practice. However, the exacted pathogenesis involved remained unclear and also lacks effective interventions. Melatonin was identified to exert protective effects for alleviating the myocardial I/R injury. This meta-analysis was determined to evaluate the efficacy of melatonin treatment against reperfusion insult and further summarize potential molecular and cellular mechanisms. METHODS AND RESULTS: 15 eligible studies with 211 animals (108 received melatonin and 103 received vehicle) were included after searching the databases of PubMed, MEDLINE, Embase, and Cochrane. Pretreatment with melatonin was associated with a significant lower infarct size in comparison with vehicle in myocardial I/R damage (WMD: -20.45, 95% CI: -25.43 to -15.47, p < 0.001; I 2 = 91.4%, p < 0.001). Evidence from subgroup analyses and sensitivity analysis indicated the robust and consistent cardioprotective effect of melatonin, while the metaregression also did not unmask any significant interactions between the pooled estimates and covariates (i.e., sample size, state, species, study type, route of administration, and duration of reperfusion, along with timing regimen of pretreatment). Accordingly, melatonin evidently increased EF (WMD: 17.19, 95% CI: 11.08 to 23.29, p < 0.001; I 2 = 77.0%, p < 0.001) and FS (WMD: 14.18, 95% CI: 11.22 to 17.15, p < 0.001; I 2 = 3.5%, p = 0.387) in the setting of reperfusion damage. CONCLUSIONS: Melatonin preadministration conferred a profound cardioprotection against myocardial I/R injury in preclinical studies.

Islet transplantation attenuates cardiac fibrosis in diabetic rats through inhibition of TGF-ß1/Smad3 pathway.

Although islet transplantation has been identified as a promising endocrine replacement treatment for patient with diabetes mellitus (DM), it still remains unclear whether islet transplantation can inhibit the diabetic-induced myocardial injury and subsequent adverse ventricular remodeling. Here, we sought to explore the molecular mechanism underlying the cardioprotective effect of islet transplantation. We established the diabetic rat model by intraperitoneal injection of STZ, which was followed by either islet transplantation or conventional insulin treatment. Compared with insulin treatment, islet transplantation further reduced the elevated blood glucose which was nearly restored to normoglycaemia. In addition, islet transplantation attenuated the increased levels of cTn-I and CK-MB, cleaved-caspase-3 in response to DM, and ameliorated diabetic-induced cardiac hypertrophy and interstitial fibrosis, along with improved extracellular matrix (ECM) deposition. Moreover, diabetic rats that underwent islet transplantation had lower expression of TGF-ß1 and lower phosphorylation levels of Smad3. Therefore, islet transplantation exerted protective effect against diabetic-induced myocardial injury and fibrotic remodeling through deactivation of TGF-ß1/Smad3 signaling pathway.

Protective role of retinoid X receptor in H9c2 cardiomyocytes from hypoxia/reoxygenation injury in rats.

BACKGROUND: Retinoid X receptor (RXR) plays a central role in the regulation of intracellular receptor signaling pathways. The activation of RXR has protective effect on H2O2-induced apoptosis of H9c2 ventricular cells in rats. But the protective effect and mechanism of activating RXR in cardiomyocytes against hypoxia/reoxygenation (H/R)-induced oxidative iniury are still unclear. METHODS: The model of H/R injury was established through hypoxia for 2 hours and reoxygenation for 4 hours in H9c2 cardiomyocytes of rats. 9-cis-retinoic acid (9-cis RA) was obtained as an RXR agonist, and HX531 as an RXR antagonist. Cultured cardiomyocytes were randomly divided into four groups: sham group, H/R group, H/R+9-cis RA -pretreated group (100 nmol/L 9-cis RA), and H/R+9-cis RA+HX531-pretreated group (2.5 µmol/L HX531). The cell viability was measured by MTT, apoptosis rate of cardiomyocytes by flow cytometry analysis, and mitochondrial membrane potential (ΔΨm) by JC-1 fluorescent probe, and protein expressions of Bcl-2, Bax and cleaved caspase-9 with Western blotting. All measurement data were expressed as mean±standard deviation, and analyzed using one-way ANOVA and the Dunnett test. Differences were considered significant when P was <0.05. RESULTS: Pretreatment with RXR agonist enhanced cell viability, reduced apoptosis ratio, and stabled ΔΨm. Dot blotting experiments showed that under H/R stress conditions, Bcl-2 protein level decreased, while Bax and cleaved caspase-9 were increased. 9-cis RA administration before H/R stress prevented these effects, but the protective effects of activating RXR on cardiomyocytes against H/R induced oxidative injury were abolished when pretreated with RXR pan-antagonist HX531. CONCLUSION: The activation of RXR has protective effects against H/R injury in H9c2 cardiomyocytes of rats through attenuating signaling pathway of mitochondria apoptosis.