Wengen Zhu

The HAS‐BLED Score for Predicting Major Bleeding Risk in Anticoagulated Patients With Atrial Fibrillation: A Systematic Review and Meta‐analysis

Our objective was to compare the diagnostic accuracy between the HAS‐BLED score and any of HEMORR2HAGES, ATRIA, CHADS2, or CHA2DS2‐VASc scores in anticoagulated patients with atrial fibrillation. We systematically searched the Cochrane Library, MEDLINE, PubMed, and Embase databases for relevant studies. Data were extracted and analyzed according to predefined clinical endpoints. Eleven studies were identified. Discrimination analysis demonstrates that HAS‐BLED has no significant C‐statistic differences for bleeding risk prediction compared with ATRIA or HEMORR2HAGES, but it has significant differences compared with CHADS2 or CHA2DS2‐VASc. The significant positive net reclassification improvement and integrated discrimination improvement values also show that HAS‐BLED is superior to that of any of HEMORR2HAGES, ATRIA, CHADS2, or CHA2DS2‐VASc scores. According to calibration analysis of HAS‐BLED, it overpredicts the risk of bleeding in the low (risk ratio [RR]: 1.16, 95% confidence interval [CI]: 0.63‐2.13, P = 0.64) risk stratification but underpredicts that in the moderate (RR: 0.66, 95% CI: 0.51‐0.86, P = 0.002) and high (RR: 0.88, 95% CI: 0.70‐1.10, P = 0.27) risk stratifications. The HAS‐BLED score not only performs better than the HEMORR2HAGES and ATRIA bleeding scores, but it also is superior to the CHADS2 and CHA2DS2‐VASc stroke scores for bleeding prediction. The HAS‐BLED score should be the optimal choice to assess major bleeding risk in clinical practice.

Association of smoking with the risk of incident atrial fibrillation: A meta-analysis of prospective studies☆

BACKGROUND Several studies have investigated the role of smoking in incident atrial fibrillation (AF) but have reported contradictory results. Identifying the quantitative association between smoking and AF risk is important for AF management and prevention; therefore, we aimed to estimate the association of smoking with incident AF. METHODS We systematically retrieved relevant studies reporting on the association between smoking and AF using the Cochrane Library, PubMed, and Embase databases. The data were extracted from applicable articles, and we used a random effects model to pool the effect estimates. RESULTS Sixteen prospective studies with an overall number of 286,217 participants and 11,878 AF cases met the inclusion criteria. A higher prevalence of AF was confirmed among smokers (risk ratio [RR]=1.23, 95% confidence interval [CI] 1.08-1.39; P=0.001). These results were stable in the sensitivity analysis. The pooled RRs showed consistent positive associations in most subgroups. Specifically, 8 articles compared both current smokers (RR=1.39, 95% CI 1.11-1.75) and former smokers (RR=1.16, 95% CI: 1.00-1.36) with never smokers. Four articles compared ever smokers (pooled RR=1.21, 95% CI 0.93-1.57) with never smokers, and 7 articles compared current smokers (pooled RR=1.21, 95% CI 1.03-1.42) with non-current smokers. Additionally, we estimated that 6.7% of the total risk of AF in men and 1.4% of the risk in women were attributable to smoking worldwide. CONCLUSIONS Based on the published literature, smoking is associated with a modest increased risk of incident AF. Smoking cessation seemed to reduce but not entirely eliminate the excess risk of AF.

Sex Differences in the Association Between Regular Physical Activity and Incident Atrial Fibrillation: A Meta-analysis of 13 Prospective Studies

Several studies investigated the role of physical activity in atrial fibrillation (AF), but the results remain controversial. We aimed to estimate the association between physical activity and incident AF, as well as to determine whether a sex difference existed. We systematically retrieved relevant studies from Cochrane Library, PubMed, and ScienceDirect through December 1, 2015. Data were abstracted from eligible studies and effect estimates pooled using a random‐effects model. Thirteen prospective studies fulfilled inclusion criteria. For primary analysis, neither total physical activity exposure (relative risk [RR]: 0.98, 95% confidence interval [CI]: 0.90‐1.06, P = 0.62) nor intensive physical activity (RR: 1.07, 95% CI: 0.93‐1.25, P = 0.41) was associated with a significant increased risk of AF. In the country‐stratified analysis, the pooled results were not significantly changed. However, in the sex‐stratified analysis, total physical activity exposure was associated with an increased risk of AF in men (RR: 1.18, 95% CI: 1.02‐1.37), especially at age <50 years (RR: 1.58, 95% CI: 1.28‐1.95), with a significantly reduced risk of AF in women (RR: 0.92, 95% CI: 0.87‐0.97). Additionally, male individuals with intensive physical activity had a slightly higher (although statistically nonsignificant) risk of developing AF (RR: 1.12, 95% CI: 0.99‐1.28), but there was a significantly reduced risk of incident AF in women (RR: 0.92, 95% CI: 0.86‐0.98). Published literature supports a sex difference in the association between physical activity and incident AF. Increasing physical activity is probably associated with an increased risk of AF in men and a decreased risk in women.

Genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy caused by desmosomal gene mutations: A systematic review and meta-analysis

The relationship between clinical phenotypes and desmosomal gene mutations in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is poorly characterized. Therefore, we performed a meta-analysis to explore the genotype-phenotype relationship in patients with ARVC. Any studies reporting this genotype-phenotype relationship were included. In total, 11 studies involving 1,113 patients were included. The presence of desmosomal gene mutations was associated with a younger onset age of ARVC (32.7 ± 15.2 versus 43.2 ± 13.3 years; P = 0.001), a higher incidence of T wave inversion in V1–3 leads (78.5% versus 51.6%; P = 0.0002) or a family history of ARVC (39.5% versus 27.1%; P = 0.03). There was no difference in the proportion of males between desmosomal-positive and desmosomal-negative patients (68.3% versus 68.9%; P = 0.60). The presence of desmosomal gene mutations was not associated with global or regional structural and functional alterations (63.5% versus 60.5%; P = 0.37), epsilon wave (29.4% versus 26.2%; P = 0.51) or ventricular tachycardia of left bundle-branch morphology (62.6% versus 57.2%; P = 0.30). Overall, patients with desmosomal gene mutations are characterized by an earlier onset age, a higher incidence of T wave inversion in V1–3 leads and a strong family history of ARVC.

Potential Cardiovascular Risks of Proton Pump Inhibitors in the General Population

Proton pump inhibitors (PPIs) are the most effective gastric acid-suppressing agents and the mainstay medical therapy for a series of acid peptic diseases. In general, the safety profile of PPIs is excellent. However, with long-term drug administration, the safety and potency of PPIs has been questioned. In the cardiovascular field, drug-drug interactions related to PPIs have been identified with particular attention regarding the use of PPIs combined with clopidogrel in patients with acute coronary syndrome. Currently, cardiovascular risks from PPIs may extend from patients with coronary artery disease to the general population. This review summarizes the possible cardiovascular risks in PPI users with no history of cardiovascular diseases and discusses possible biological mechanisms.

Can ventricular tachycardia non-inducibility after ablation predict reduced ventricular tachycardia recurrence and mortality in patients with non-ischemic cardiomyopathy? A meta-analysis of twenty-four observational studies

BACKGROUND At present, the role of ventricular tachycardia (VT) non-inducibility after ablation in patients with non-ischemic cardiomyopathy (NICM) remains controversial. We conducted a meta-analysis of the published literature to assess whether VT non-inducibility after ablation could predict reduced VT recurrence and mortality in patients with NICM. METHODS PubMed, ScienceDirect, and the Cochrane library were searched for studies evaluating the effects of VT non-inducibility after catheter ablation on the long-term outcome in NICM patients with sustained VT. Results were analyzed using a fixed-effect model, and the data were pooled using RevMan 5.3 software. RESULTS Twenty-four observational studies were identified (736 participants, mean follow-up time: 22months). NICM patients with VT inducibility after ablation had a higher risk of VT recurrence (odds ratio [OR]=5.83, 95% confidence interval [CI] 4.07-8.37; P<0.00001) and all-cause mortality (OR=3.55, 95% CI 1.62-7.78; P=0.002) compared with VT non-inducibility. Similarly in the subgroup analysis, patients with VT inducibility showed a higher risk of VT recurrence from non-ischemic dilated cardiomyopathy (OR=3.92, 95% CI 2.36-6.50; P<0.00001) and arrhythmogenic right ventricular dysplasia/cardiomyopathy (OR=5.37, 95% CI 2.20-13.10; P=0.0002). Additionally, meta-analysis also showed that combined endo-epicardial ablation significantly reduced the risk of VT recurrence compared with endocardial-only ablation (OR=2.02, 95% CI 1.19-3.44; P=0.009; mean follow-up time: 22months). CONCLUSION Recent evidence has shown that VT non-inducibility after ablation is a predictor for reduced VT recurrence and mortality compared with VT inducibility in NICM patients with sustained VT. In addition, endocardial plus adjuvant epicardial ablation provides better long-term arrhythmia-free survival than endocardial ablation alone.

Fluoroquinolones increase the risk of serious arrhythmias: A systematic review and meta-analysis.

Background: The association between oral fluoroquinolones (FQs) usage and risk of severe arrhythmia-related events (ventricular arrhythmias and sudden cardiac death) remains controversial. Therefore we aimed to quantify this association and to evaluate the effects of FQs on adverse cardiovascular (CV) outcomes. Methods: We retrieved data from the Cochrane Collaboration, PubMed, and China National Knowledge Infrastructure (CNKI) databases until August 2017. The studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data were extracted from the eligible articles, and we used a random effects model to calculate the effect estimates. Results: Of the 16 studies that were included, 7 studies included serious arrhythmias, 3 studies included CV death, and 11 studies included all-cause death. The pooled RRs of FQs use were: 2.29 (95% CI: 1.20–4.36, P = .01) for serious arrhythmias; 1.60 (95% CI: 1.17–2.20, P = .004) for CV death; and 1.02 (95% CI: 0.76–1.37, P = .92) for all-cause death. The RRs associated with serious arrhythmias were 6.27 for gatifloxacin, 4.20 for moxifloxacin, 1.73 for ciprofloxacin, and 1.41 for levofloxacin. Current FQs users showed an increased risk of serious arrhythmias in the subgroup analysis. Treatment with FQs is associated with an absolute risk increase of 160 additional sudden deaths or ventricular arrhythmias, and 43 additional CV deaths per 1 million treatment courses. Conclusion: The use of FQs could increase the risk of serious arrhythmias and CV death but not increase or all-cause death. Moreover, moxifloxacin and levofloxacin showed a higher risk of serious arrhythmias.

Efficacy and safety of triple versus dual antithrombotic therapy in atrial fibrillation and ischemic heart disease: a systematic review and meta-analysis

The optimal antithrombotic regimen for patients with atrial fibrillation and ischemic heart disease remains unclear. Therefore, we aimed to compare the efficacy and safety of triple therapy (TT [an anticoagulant and 2 antiplatelet drugs]) with dual therapy (DAPT [2 antiplatelet drugs] or DT [an anticoagulant and a single antiplatelet drug]) in patients with atrial fibrillation and ischemic heart disease. We systematically searched the Cochrane Library, PubMed and Embase databases for all relevant studies up to August 2017. The overall risk estimates were calculated using the random-effects model. A total of 17 observational studies were included. Regarding the efficacy outcomes, no differences were observed between the triple therapy and the dual therapy for all-cause death, cardiovascular death, or thrombotic complications (i.e., acute coronary syndrome, stent thrombosis, thromboembolism/stroke, and major adverse cardiac and cerebrovascular events). Regarding the safety outcomes, compared with DAPT, TT was associated with increased risks of major bleeding (a relative risk of 1.96 [1.40–2.74]), minor bleeding (1.69 [1.06–2.71]) and overall bleeding (1.80 [1.23–2.64]). Compared wtih DT, TT was associated with a greater risk of major bleeding (1.65 [1.23–2.21]), but rates of minor bleeding (0.99 [0.56–1.77]) and overall bleeding (1.14 [0.76–1.71]) were similar. Overall, TT confers an increased hazard of major bleeding with no thromboembolic protection compared with dual therapy in patients with atrial fibrillation and ischemic heart disease.

Association of Physical Fitness With the Risk of Atrial Fibrillation: A Systematic Review and Meta‐Analysis

Several studies have investigated the role of physical fitness in atrial fibrillation (AF), but the results remain controversial. We aimed to estimate the association between physical fitness and risk of AF. We comprehensively retrieved data from the Cochrane Library, PubMed, and Embase databases until February 29, 2016, for studies evaluating the association of physical fitness with the risk of AF. Data were abstracted from included studies, and effect estimates were pooled using a random‐effects model. Six studies with a total of 205 094 participants and 15 919 AF cases fulfilled the inclusion criteria. When physical fitness was assessed as a continuous variable, per incremental increase of physical fitness was associated with a 9% reduced risk of AF (risk ratio [RR]: 0.91, 95% confidence interval [CI]: 0.84‐1.00, P = 0.05). When physical fitness was assessed as a categorical variable, the risk of AF was significantly reduced (RR: 0.51, 95% CI: 0.28‐0.91, P = 0.02) in individuals with the highest level of physical fitness compared with those with the lowest level. The intermediate vs the lowest level of physical fitness was associated with a 28% reduced risk of AF (RR: 0.72, 95% CI: 0.56‐0.93, P = 0.01). The sensitivity analysis indicated that these results were stable. Notably, there was evidence of statistical heterogeneity across studies; therefore, we should interpret the results cautiously. In conclusion, published literature supports that a higher level of physical fitness is associated with a lower risk of AF. Further studies should be performed to confirm these findings.

O-GlcNAcylation of cardiac Nav1.5 contributes to the development of arrhythmias in diabetic hearts

BACKGROUND Cardiovascular complications are major causes of mortality and morbidity in diabetic patients. The mechanisms underlying the progression of diabetic heart (DH) to ventricular arrhythmias are unclear. O-linked GlcNAcylation (O-GlcNAc) is a reversible post-translational modification for the regulation of diverse cellular processes. The purpose of this study was to assess whether the cardiac voltage-gated sodium channel (Nav1.5) is subjected to O-linked GlcNAcylation (O-GlcNAc), which plays an essential role in DH-induced arrhythmias. METHODS AND RESULTS In this study, Sprague-Dawley rats (male, 200-230 g) were treated with a single high-dose of streptozotocin (STZ, 80 mg/kg) to generate a rat model of diabetes. STZ-induced 3-month diabetic rats displayed increased susceptibility to ventricular arrhythmias. The elevated O-GlcNAc modification was correlated with decreases in both total and cytoplasmic Nav1.5 expression in vivo and in vitro. In addition, both co-immunoprecipitation and immunostaining assays demonstrated that hyperglycemia could increase the O-GlcNAc-modified Nav1.5 levels and decrease the interaction between Nav1.5 and Nav1.5-binding proteins Nedd4-2/SAP-97. Furthermore, patch-clamp measurements in HEK-293 T cells showed that Nav1.5 current densities decreased by 30% after high-glucose treatment, and the sodium currents increased via O-GlcNAc inhibition. CONCLUSION Our data suggested that hyperglycemia increased the O-GlcNAc modification of Nav1.5 expression and decreased the interaction between Nav1.5 and Nedd4-2/SAP-97, which led to the abnormal expression and distribution of Nav1.5, loss of function of the sodium channel, and prolongation of the PR/QT interval. Excessive O-GlcNAc modification of Nav1.5 is a novel signaling event, which may be an underlying contributing factor for the development of the arrhythmogenesis in DH.