Preadmission metformin use increased the incidence of hyperlactatemia at admission and 30-day in-hospital mortality among T2D patients with heart disease at high risk of hypoxia.

BACKGROUND: Surprisingly, despite the high prevalence of metformin use in type 2 diabetes (T2D) patients with heart disease, limited safety data is available regarding metformin use in patients with acute and critical heart disease. METHODS: In this single-center retrospective study, patients admitted to the cardiology department for heart failure (HF) or acute coronary syndrome (ACS) between December 2013 and December 2021 and who underwent arterial blood gas analysis at admission with an estimated glomerular clearance rate of ≥45 ml/min/1.73 m2 were identified. The incidences of hyperlactatemia, acidosis, and 30-day in-hospital mortality were compared between preadmission metformin users and nonusers. RESULTS: Of 526 admissions, 193/193 metformin users/nonusers were selected in a propensity score-matched model. Metformin users had greater lactate levels (2.55 ± 2.07 mmol/l vs. 2.00 ± 1.80 mmol/l P < 0.01), a greater incidence of hyperlactatemia [odds ratio (OR) = 2.55; 95% confidence interval (CI), 1.63-3.98; P < 0.01] and acidosis (OR = 1.78; 95% CI, 1.00-3.16; P < 0.05) at admission and a greater incidence of in-hospital mortality (OR = 3.83; 95% CI, 1.05-13.94; P < 0.05), especially those with HF/acute myocardial infarction, elderly age, or without preadmission insulin use. CONCLUSIONS: Our results suggest that, compared to metformin nonusers, preadmission use of metformin may be associated with a greater incidence of hyperlactatemia and acidosis at admission and greater 30-day in-hospital mortality among T2D patients with HF or ACS at high risk of hypoxia, particularly those without preadmission insulin use. The safety of metformin in this population needs to be confirmed in prospective controlled trials.

Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis.

ABSTRACT: The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

Comparative Effectiveness and Safety of Milrinone and Levosimendan as Initial Inotrope Therapy in Patients With Acute Heart Failure With Renal Dysfunction.

ABSTRACT: Levosimendan and milrinone are 2 effective inotropic drugs used to maintain cardiac output in acute heart failure (AHF). Using data from patients with AHF with and without abnormal renal function, we performed this single-center, retrospective cohort study to compare the effectiveness and safety of milrinone and levosimendan for the initial management of AHF. Patients admitted for heart failure between December 2016 and September 2019 who received levosimendan or milrinone as initial inotrope therapy in the cardiology department were identified. A total of 436 levosimendan and 417 milrinone patients with creatinine clearance (CrCl) ≥30 mL/min and 50 levosimendan and 71 milrinone patients with CrCl <30 mL/min or on dialysis were included. The primary outcome was a composite of changes in clinical status at 15 and 30 days after initial inotrope therapy discontinuation. Between subgroups of patients with CrCl ≥30 mL/min, there were no significant differences in primary outcomes; milrinone was associated with more frequent hypotension and cardiac arrhythmias during the infusion period (P < 0.01), while levosimendan was associated with more frequent cardiac arrhythmias within 48 hours after discontinuation (P < 0.05). Of the patients with CrCl <30 mL/min or on dialysis, more initial levosimendan than milrinone patients and those who switched to alternative inotropes experienced clinical worsening at 15 days and 30 days (P < 0.05). According to our results, patients with AHF with severe renal dysfunction should avoid initial inotrope therapy with levosimendan.

Optomechanical design of a wide-field auroral imager on Fengyun-3D.

We present the optomechanical design and development of a wide-field auroral imager (WAI) on board the satellite Fengyun-3D. The optomechanical system of the WAI features a combination of a large field of view and a single-axis scanning mechanism. The combination makes the WAI perform better than its counterparts in temporal resolution in a low Earth orbit. In-orbit tests have verified the survival of WAI in the launching vibration and space environment. It has functioned on-orbit since 2018, with a spatial resolution of ∼10km at the nadir point, at a reference height of 110 km above the ionosphere.

Ivabradine and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: This was a meta-analysis of randomized control trials (RCTs) to evaluate the effect of ivabradine on the risk of atrial fibrillation (AF) and its effect on the ventricular rate in patients with AF. The PubMed, EMBASE, Cochrane Controlled Trials Register, and other databases were searched for RCTs on ivabradine. Thirteen trials with 37,533 patients met the inclusion criteria. The incidence of AF was significantly higher in the ivabradine treatment group than in the control group [odds ratio (OR), 1.23; 95% confidence interval (CI), 1.08-1.41], although it was reduced after cardiac surgery (OR, 0.70; 95% CI, 0.23-2.12). Regarding left ventricular ejection fraction (LVEF), ivabradine increased the risk of AF in both LVEF >40% (OR, 1.42; 95% CI, 1.24-1.63) and LVEF ≤40% subgroups (OR, 1.16; 95% CI, 0.98-1.37). The risk of AF was increased by both small and large cumulative doses of ivabradine (small cumulative dose: OR, 3.00; 95% CI, 0.48-18.93; large cumulative dose: OR, 1.05; 95% CI, 0.83-1.34). Furthermore, ivabradine may reduce the ventricular rate in patients with AF. In conclusion, we found that both large and small cumulative doses of ivabradine were associated with an increased incidence of AF, and the effect was more marked in the LVEF >40% subgroup. Nevertheless, ivabradine therapy is beneficial for the prevention of postoperative AF. Furthermore, ivabradine may be effective in controlling the ventricular rate in patients with AF, although more RCTs are needed to support this conclusion.

Association of dipeptidyl peptidase IV polymorphism, serum lipid profile, and coronary artery stenosis in patients with coronary artery disease and type 2 diabetes.

ABSTRACT: Cardiovascular disease (CAD) is a devastating illness, but to date there are limited means of predicting a person's coronary stenosis severity and their prognosis. The study was performed to investigate the relationship between dipeptidyl peptidase 4(DPP4) gene polymorphisms and serum lipid profiles, as well as the severity of coronary artery stenosis in patients with CAD and type 2 diabetes (T2DM) for the first time.Herein, 201 patients with CAD and T2DM were enrolled in the Department of Cardiology, Shandong Provincial Qianfoshan Hospital. DPP4 rs3788979 and rs7608798 single nucleotide polymorphisms (SNPs) were genotyped. The general information of all patients was collected, and the associations between DPP4 SNPs and lipid profiles were detected. At the same time, association between SNP polymorphisms and the degree of coronary artery stenosis were analyzed.There was a significant difference in apolipoprotein B (ApoB) levels (P = .011) for the rs3788979 polymorphism, while no difference was identified in other blood lipids or with other mutations. SNP mutation of A to G in rs3788979 was associated with a reduced percentage of severe coronary artery stenosis in female patients (P = .023) as well as those with nosmoking (P = .030), nodrinking (P = 0.007), and nocardiovascular family history (P = 0.015).G allele of rs3788979 is associated with a reduced ApoB level. Besides, we suggest that G allele in rs3788979 may have a cardioprotective effect and prove to be a useful and specific measure when predicting a patient's coronary stenosis severity if diagnosed with CAD and T2DM.

Wide-field auroral imager onboard the Fengyun satellite.

The newly launched Fengyun-3D (FY-3D) satellite carried a wide-field auroral imager (WAI) that was developed by Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences (CIOMP), which will provide a large field of view (FOV), high spatial resolution, and broadband ultraviolet images of the aurora and the ionosphere by imaging the N2 LBH bands of emissions. The WAI consists of two identical cameras, each with an FOV of 68° in the along-track direction and 10° in the cross-track direction. The two cameras are tilted relative to each other to cover a fan-shaped field of size 130° × 10°. Each camera consists of an unobstructed four-mirror anastigmatic optical system, a BaF2 filter, and a photon-counting imaging detector. The spatial resolution of WAI is ~10 km at the nadir point at a reference height of 110 km above the Earth's surface. The sensitivity is >0.01 counts s-1 Rayleigh-1 pixel-1 (140-180 nm) for both cameras, which is sufficient for mapping the boundaries and the fine structures of the auroral oval during storms/substorms. Based on the tests and calibrations that were conducted prior to launch, the data processing algorithm includes photon signal decoding, geometric distortion correction, photometric correction, flat-field correction, line-of-sight projection and correction, and normalization between the two cameras. Preliminarily processed images are compared with DMSP SSUSI images. The agreement between the images that were captured by two instruments demonstrates that the WAI and the data processing algorithm operate normally and can provide high-quality scientific data for future studies on auroral dynamics.

Combination Use of Clopidogrel and Proton Pump Inhibitors Increases Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis.

BACKGROUND: Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACEs). This has been a highly controversial topic for years. DESIGN: The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs is associated with increased risk of MACEs than with clopidogrel alone in patients with coronary artery disease. METHODS: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs) were combined using a random-effects model. RESULTS: Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn't. CONCLUSION: The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated with significantly increased MACE in patients coadministered with clopidogrel.

Association between DPP4 gene polymorphism and serum lipid levels in Chinese type 2 diabetes individuals.

OBJECTIVE: The goal of the genetic investigation was to identify the associations of serum lipid levels and DPP-4 variants in Chinese type 2 diabetes patients. METHODS: We detected four variants of the DPP4 gene in 190 Chinese individuals with type 2 diabetes and tested for an association with dyslipidemia in 82 selected samples. Data including basic information, HbA1c, FPG, serum lipid parameters were collected. Statistical analysis was performed by SPSS 13.0 through ANOVA and χ2 test. RESULTS: The genetic polymorphism of rs4664443, rs3788979, rs7608798 and rs1558957 in Chinese type 2 diabetes were consistent with Hardy-Weinberg equilibrium. The CT genotype of rs4664443 suffered from higher serum TG (P=0.013), LDL (P=0.044) and ApoB (P=0.006) levels, whereas the TT genotype of rs7608798 exhibited a lower serum TG level (P=0.037). For rs3788979, the serum TG level (P=0.034) and BMI (P=0.04) were significantly different among genotypes. Moreover, serum TG and TC levels and BMI showed a positive correlation with the number unfavorable alleles, and individuals with more than two unfavorable alleles had higher TG (P=0.004), TC (P=0.011), and BMI (P=0.044) values. CONCLUSIONS: This is the first study to investigate DPP4 allelic distributions and their association with dyslipidemia in Chinese type 2 diabetes patients, which may have clinical significance.

Long-Term Effects of Atrial Ganglionated Plexi Ablation on Function and Structure of Sinoatrial and Atrioventricular Node in Canine.

BACKGROUND: Long-term effects of ganglionated plexi (GP) ablation on sinoatrial node (SAN) and atrioventricular node (AVN) remain unclear. This study is to investigate the long-term effects of ablation of cardiac anterior right GP (ARGP) and inferior right GP (IRGP) on function and structure of SAN and AVN in canine. METHODS: Thirty-two dogs were randomly divided into an operated group (n = 24) and sham-operated group (n = 8). ARGP and IRGP were ablated in operated group which was randomly divided into three subgroups according to the period of evaluation after operation (1 month, 6 months, 12 months). The functional and histological characteristics of SAN and AVN, as well as the expression of connexin (Cx) 43 and Cx 45 in SAN and AVN, were evaluated before and after ablation. RESULTS: Resting heart rate was increased and AVN effective refractory period was prolonged and sinus node recovery time (SNRT) and corrected SNRT were shortened immediately after ablation. These changes were reverted to preablation level after 1 month. At 1 month, ventricular rate during atrial fibrillation was slowed, atria-His intervals were prolonged, and Cx43 and Cx45 expression in SAN and AVN were downregulated. At 6 months, all changes were reverted to preablation level. The histological characteristics of SAN and AVN did not change. CONCLUSION: Ablation of ARGP and IRGP has short-term effects on function and structure of SAN and AVN rather than long-term effects, which suggests that ablation of ARGP and IRGP is safe. Atrioventricular conduction dysfunction after ablation may be related to downregulated Cx43 and Cx45 expression in AVN.

Long-Term Effects of Ganglionated Plexi Ablation on Electrophysiological Characteristics and Neuron Remodeling in Target Atrial Tissues in a Canine Model.

BACKGROUND: The long-term effects of ganglionated plexi ablation on electrophysiological characteristics and neuron remodeling in target atrial tissues remain unclear. METHODS AND RESULTS: Dogs in group 1 (control, n=8) were not subjected to ganglionated plexi ablation and observed for 1 month, and dogs in groups 2 to 4 (ablation groups, n=8 each) underwent ablation of the right-sided ganglionated plexi and observed for 1, 6, and 12 months, respectively. Atrial electrophysiological characteristics were examined before ablation, immediately and continuously after ablation. Target atrial tissues were subjected to immunohistochemical staining and Western blot analysis. Atrial effective refractory period was significantly prolonged immediately after ablation (P<0.001), and persisted for 1 month (P<0.05). Nerve densities decreased 1 month after ablation (P<0.001). These parameters reverted to preablation levels after 6 and 12 months. In the ablation groups, atrial fibrillation was induced in 5 of 8 dogs after 1 month and in all animals after 6 and 12 months. Atrial fibrillation was not observed in the control group and in the experimental groups immediately after ablation. Moreover, the expression of the growth-associated protein 43 was upregulated after ablation. CONCLUSIONS: Ganglionated plexi ablation effectively prolonged atrial effective refractory period for a short period, but the long-term effects on atrial effective refractory period and the suppression of atrial fibrillation induction were not persistent. Targeted atrial neuron remodeling may be an important mechanism underlying the observed electrophysiological changes.

MicroRNA profiling of atrial fibrillation in canines: miR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1.

BACKGROUND: A critical mechanism in atrial fibrillation (AF) is cardiac autonomic nerve remodeling (ANR). MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Numerous miRNAs are involved in diseases of the nervous and cardiovascular systems. OBJECTIVE: We aimed to assess the underlying role of miRNAs in regulating cardiac ANR in AF by right atrial tachypacing (A-TP) in canines. METHODS AND RESULTS: Following 4-week A-TP, the superior left ganglionated plexuses (SLGPs), which are embedded in the fat pads of the left atrium, were subjected to miRNA expression profiling to screen preferentially expressed miRNAs. Sixteen miRNAs showed significantly differential expression between the control and A-TP groups, including miR-206, miR-203, miR-224 and miR-137. In particular, we focused on miR-206, which was elevated ~10-fold in A-TP dogs. Forced expression of miR-206 through lentiviral infection based on A-TP in vivo significantly shortened the atrial effective refractory period (AERP) (81 ± 7 vs. 98 ± 7 ms, P < 0.05). Immunohistochemical analysis showed that the regeneration of nerves increased more than 2-fold by miR-206 overexpression (P < 0.01). The expression of superoxide dismutase 1 (SOD1) was repressed by miR-206 overexpression by Western blot and luciferase assay, indicative of SOD1 as a direct target of miR-206. Overexpression of miR-206 increased reactive oxygen species (ROS) levels in vitro and in vivo, whereas miR-206 silencing attenuated irradiation- or A-TP-induced ROS. Knockdown of SOD1 effectively abolished ROS reduction caused by miR-206 silencing. CONCLUSIONS: Our results found the differential expression of miRNAs in response to ANR in AF and elucidated the important role of miR-206 by targeting SOD1. The study illustrated the novel molecular mechanism of ANR and indicated a potential therapeutic target for AF.

The safety and efficacy of antithrombotic therapy in patients undergoing cardiac rhythm device implantation: a meta-analysis.

AIMS: The meta-analysis was to assess the safety and efficacy of periprocedural antithrombotic therapy and to evaluate the risk factors potentially associated with bleeding among patients undergoing cardiac implantable electronic devices implantations. METHODS AND RESULTS: A systematic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register was performed. Anticoagulation and antiplatelet therapies were assessed separately. Uninterrupted anticoagulation was associated with significant lower bleeding risk compared with heparin bridging strategy [odds ratio (OR) = 0.31, 95% confidence interval (CI) 0.18-0.53, and P < 0.0001], but there was no significant difference in thromboembolic risk between these two strategies (OR = 0.82, 95% CI 0.32-2.09, and P = 0.65). The haematoma rate was significantly increased in dual antiplatelet therapy group (OR = 6.84, 95% CI 4.16-11.25, and P < 0.00001), but not in single antiplatelet therapy (OR = 1.52, 95% CI 0.93-2.46, and P = 0.09). Clopidogrel increased the risk of haematoma vs. aspirin (OR = 2.91, 95% CI 1.27-6.69, and P = 0.01). Otherwise, a lower risk of haematoma was observed in pacemaker group vs. cardiac resynchronization therapy and/or implantable cardioverter defibrillator group (OR = 0.64, 95% CI 0.50-0.82, and P = 0.0004). CONCLUSION: This meta-analysis suggested that uninterrupted oral anticoagulation seems to be the better strategy, associated with a lower risk of bleeding complications rather than heparin bridging, and dual antiplatelet therapy carried a significant risk of bleeding whereas single antiplatelet therapy was relatively safe among patients undergoing cardiac implantable electronic devices implantations. Meanwhile, cardiac resynchronization therapy and/or implantable cardioverter defibrillator implantations increase the bleeding.

Effects of radiofrequency catheter ablation on left ventricular structure and function in patients with atrial fibrillation: a meta-analysis.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). This study was designed to investigate the effects of RFCA on left ventricular (LV) structure and function in AF patients. METHODS AND RESULTS: A systematic literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed to identify trials involving changes of LV structure and function in AF patients undergoing RFCA. Effect size was expressed as weighted mean difference (WMD) with 95% confidence interval (CI). LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were estimated. A total of 21 trials including 1,135 participants were qualified for this meta-analysis. Compared to the baseline values, there were significant decreases in LVEDV (WMD, -6.39 ml; 95%CI, -12.46 to -0.33) and LVESV (WMD, -6.39 ml; 95%CI, -11.35 to -1.42) and a significant improvement in LVEF (WMD, 6.23%; 95%CI, 3.70 to 8.75), but no significant changes were observed in LVEDD (WMD, -0.64 mm; 95%CI, -2.40 to 1.13) and LVESD (WMD, -0.38 mm; 95%CI, -1.32 to 0.56) after RFCA. Subgroup analysis demonstrated that patients with low LVEF (WMD, 11.90%; 95%CI, 9.16 to 14.64) gained more benefits than those with normal LVEF (WMD, 1.56%; 95%CI, 0.38 to 2.74). Besides, patients with chronic AF (WMD, 10.96%; 95%CI, 4.92 to 17.01) improved more than those with paroxysmal AF (WMD, 1.93%; 95%CI, -0.27 to 4.12). CONCLUSIONS: RFCA in AF patients could reverse LV structural remodeling and improve LV systolic function, especially in patients with low LVEF and chronic AF.

Autonomic neural remodeling of the pulmonary vein-left atrium junction in a prolonged right atrial pacing canine model.

BACKGROUND: No evidence has been presented to show whether autonomic neural remodeling occurs in pulmonary vein-left atrium (PV-LA) junction and what an important role it may play in AF. This study aims to find out these issues in a prolonged rapid atrial pacing canine model. METHODS: Twelve healthy mongrel dogs were randomly divided into two groups, six in each: the paced group underwent rapid right atrial pacing at 400 beats per minute for 4 weeks, and the control group was not paced. The effective refractory period (ERP) of left superior pulmonary vein-left atrium (LSPV-LA) junction in all animals was determined immediately after 4 weeks. Tissues were removed from 1 cm around all PV-LA junctions. Immunohistochemical staining and western blotting were performed to examine the expression of tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). RESULTS: Compared with the control group, ERP of LSPV-LA junction of the paced group was significantly shortened ([83.33 ± 16.33] ms vs [111.67 ± 20.41] ms, P < 0.05). Spontaneous atrial fibrillation developed in two animals in the paced group, but in none of the control group. Immunohistochemistry showed that the average density and heterogeneity of both TH- and ChAT-positive nerves at LSPV-LA junction in the paced group were significantly higher compared to the control group (P < 0.01). Western blotting showed that the expression of TH and ChAT at four PV-LA junctions in the paced group also increased markedly compared with the control group (P < 0.01). CONCLUSION: Autonomic neural remodeling did exist in PV-LA junction after prolonged atrial pacing, which may contribute to the initiation of atrial fibrillation and be significant in its treatment by radiofrequency catheter ablation.

Renin-angiotensin system inhibitors prevent the recurrence of atrial fibrillation: a meta-analysis of randomized controlled trials.

OBJECTIVE: This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). METHODS: A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed to identify randomized controlled trials involving the prevention of recurrence of AF with renin-angiotensin system blockade therapy. Subgroup analysis and meta-regression were performed. Publication bias was checked through funnel plot and Egger's test. RESULTS: Twenty-one randomized controlled trials including 13,184 patients with AF were identified. Overall, the recurrence of AF was significantly reduced in patients using ACEI/ARBs [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.56; P < 0.00001], especially both in irbesartan subgroup (OR, 0.38; 95% CI, 0.21-0.68; P = 0.001) and in patients receiving antiarrhythmic drug (AAD) (OR, 0.37; 95% CI, 0.29-0.48; P < 0.00001), and there was no significant difference between ACEIs and ARBs (ACEIs: OR, 0.42; 95% CI, 0.31-0.57 and ARBs: OR, 0.42; 95% CI, 0.31-0.57). Moreover, it was found that the benefits of ACEI/ARBs revealed positive correlation to systolic blood pressure (regression coefficient: -0.0700257, P = 0.000) in no-AAD users. CONCLUSIONS: ACEI/ARBs are effective on the secondary prevention of AF, especially in patients receiving AAD and suffering from hypertension.

An altered expression of genes involved in the regulation of ion channels in atrial myocytes is correlated with the risk of atrial fibrillation in patients with heart failure.

The aim of this study was to investigate the correlation between the altered expression of genes involved in the regulation of ion channels in atrial myocytes and the risk of atrial fibrillation (AF) in patients with heart failure (HF). Right atrial appendages were obtained from 18 HF patients and 18 patients with normal cardiac functions who had undergone surgery. The mRNA expression levels of Kv4.3α, KvLQT1, Kv1.5, L-Caα1c and NCX were measured by reverse transcription-PCR (RT-PCR). Protein expression levels were also detected by western blotting. In comparison with the control group exhibiting normal cardiac functions, the mRNA and protein expression levels of Kv4.3α, KvLQT1 and L-Caα1c were significantly reduced in HF patients. By contrast, the mRNA and protein expression levels of NCX were significantly increased in HF patients compared with the control group (P<0.01). The mRNA expression levels of Kv1.5 were not evidently altered. We demonstrated that increased levels of Kv4.3α, KvLQT1 and L-Caα1c and decreased levels of NCX are correlated with the risk of AF in HF patients. Changes in the gene expression of ion channel-related proteins may therefore be used as biological markers of AF occurring in HF patients in future studies.

MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model.

BACKGROUND: The potential mechanisms of microRNA-1 (miR-1) in the electrical remodeling of atrial fibrillation remain unclear. The purpose of this study was to evaluate the effects of miR-1 on the atrial effective refractory period (AERP) in a right atrial tachypacing model and to elucidate the potential mechanisms. METHODS AND RESULTS: QRT-PCR and western blot were used to detect the expression of the miR-1, KCNE1, and KCNB2 genes after 1-week of right atrial tachypacing in New Zealand white rabbits. The AERP was measured using a programmable multichannel stimulator, and atrial fibrillation was induced by burst stimulation in vivo. The slowly activating delayed rectifier potassium current (IKs) and AERP in atrial cells were measured by whole cell patch clamp in vitro. Right atrial tachypacing upregulated miR-1 expression and downregulated KCNE1 and KCNB2 in this study, while the AERP was decreased and the atrial IKs increased. The downregulation of KCNE1 and KCNB2 levels was greater when miR-1 was further upregulated through in vivo lentiviral infection. Electrophysiological tests indicated a shorter AERP, a great increase in the IKs and a higher atrial fibrillation inducibility. In addition, similar results were found when the levels of KCNE1 and KCNB2 were downregulated by small interfering RNA while keeping miR-1 level unaltered. Conversely, knockdown of miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs. KCNE1 and KCNB2 as the target genes for miR-1 were confirmed by luciferase activity assay. CONCLUSIONS: These results indicate that miR-1 accelerates right atrial tachypacing-induced AERP shortening by targeting potassium channel genes, which further suggests that miR-1 plays an important role in the electrical remodeling of atrial fibrillation and exhibits significant clinical relevance as a potential therapeutic target for atrial fibrillation.

Efficacy of cardiac autonomic denervation for atrial fibrillation: a meta-analysis.

INTRODUCTION: Adjunctive complex fractionated atrial electrograms (CFAE) ablation or ganglionated plexi (GP) ablation have been proposed as new strategies to increase the elimination of AF, but the difference between CFAE/GP ablation and pulmonary vein isolation (PVI), as well as the combined effect of CFAE/GP plus PVI ablation were unclear. This meta-analysis was designed to determine whether adjunctive cardiac autonomic denervation (CAD) was effective for the elimination of AF, and whether CAD alone was superior to PVI in AF patients. METHODS: A systemic literature search in MEDLINE, EMBASE, and Cochrane Controlled Trials Register (CCRT) was performed and controlled trials comparing the effect of PVI plus CFAE/GP ablation with PVI, as well as CFAE/GP ablation with PVI were collected. RESULTS: A total of 15 trials including 1,147 patients with AF were qualified for this meta-analysis. CAD plus PVI significantly increased the freedom from AF/ATs (OR 1.85, 95% CI: 1.33-2.59, P = 0.29). Subgroup analysis showed that additional CAD increased the ratio of sinus rhythm maintenance in both paroxysmal AF (OR 1.69; 95% CI: 1.09-2.62, P = 0.41) and nonparoxysmal AF (OR 2.11, 95% CI: 1.14-3.90, P = 0.14). Besides, when compared respectively, adjunctive CAD was not superior to PVI (OR 0.31; 95% CI: 0.11-0.86, P = 0.002). CONCLUSION: This study suggested that CAD plus PVI significantly increase the freedom from recurrence of AF both in paroxysmal and nonparoxysmal patients. However, when compared alone, the benefit of CAD was not superior to PVI.

Statin therapy for the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: To assess the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) for primary and secondary prevention of atrial fibrillation, and to evaluate the efficacy of individual statins and their dosages. DESIGN: Meta-analysis of 20 randomized controlled trials. PATIENTS: A total of 32,311 patients who received either a statin (16,203 patients) or a placebo or active control regimen (16,108 patients) for either primary or secondary prevention of atrial fibrillation as part of a research study. MEASUREMENTS AND MAIN RESULTS: A systemic literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register was performed to identify randomized controlled trials involving the prevention of atrial fibrillation with statin therapy. Effect size was expressed as odds ratio (OR) with 95% confidence interval (CI). Subgroup analysis was performed to explore the reasons for heterogeneity. Of the 20 trials, atorvastatin was studied in 11, pravastatin in five, rosuvastatin in three, and simvastatin in one. Overall, among the 32,311 patients in these trials, the risk of atrial fibrillation was significantly reduced by statins (OR 0.59, 95% CI 0.45-0.76), and the drugs were effective for both primary prevention (OR 0.67, 95% CI 0.51-0.88) and secondary prevention (OR 0.40, 95% CI 0.20-0.83). Secondary prevention was not superior to primary prevention, however. A significant benefit was observed in the atorvastatin-treated subgroup (OR 0.43, 95% CI 0.27-0.66), especially in the dose range of 10-40 mg/day (OR 0.29, 95% CI 0.19-0.45). No protective effect was observed in the pravastatin subgroup (OR 1.03, 95% CI 0.77-1.37). CONCLUSION: This meta-analysis suggests that statin therapy is useful for the prevention of atrial fibrillation. The benefit of statins in secondary prevention was significant but not superior to primary prevention. Atorvastatin was more effective than pravastatin, and its effects were dose related, with lower doses being more effective. The number of trials focusing on individual drugs is still insufficient, and more randomized controlled trials are necessary to further support these conclusions.