Kun Lin

Relative efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation by network meta-analysis

Background Much direct evidence has proved that the novel oral anticoagulants (NOACs) are noninferior or superior to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation, and lead to a relevant decrease in bleeding profiles. However, no study has compared NOACs with each other head-to-head. The current study is a network meta-analysis aiming to assess the efficacy and safety of NOACs. Methods Cochrane library, Pubmed NCBI, EMBASE and MEDLINE were systematically searched for randomized controlled trials that assessed the efficacy and safety profiles of NOACs compared with warfarin. The primary outcome was the rate of stroke or systemic embolism, and the secondary outcome was the rate of bleeding events. Network meta-analysis was performed using Markov chain Monte Carlo methods. Results A total of four phase III randomized controlled trials (n = 71683) met the inclusion criteria. All NOACs except low dose of edoxaban showed noninferior efficacies to warfarin in stroke prevention. In the field of hemorrhage, apixaban was safer than edoxaban 60 mg in any bleeding events and had fewer major bleeding events compared with dabigatran 150 mg and rivaroxaban. Conclusion NOACs are promising candidates for stroke prevention in patients with nonvalvular atrial fibrillation due to a favorable risk–benefit profile. All NOACs other than edoxaban 30 mg had parallel efficacies with respect to stroke prevention. Apixaban had an advantage over the other NOACs in safety.

Renal Denervation Suppresses Atrial Fibrillation in a Model of Renal Impairment

Background A close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity. Objective The main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI. Methods Unilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured. Results Embolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN. Conclusions RDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue.

Effects of Body Mass Index on Risks for Ischemic Stroke, Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial. Objective This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients. Methods Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality). Results A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m2) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m2), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m2), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05). Conclusions Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.

Proton pump inhibitors as also inhibitors of atrial fibrillation.

Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related upper digestive diseases, including gastric and duodenal ulcer and gastroesophageal reflux disease (GERD). Remarkably, several small clinical trials have shown that these drugs also reduce the symptoms and frequency of atrial fibrillation (AF) episodes in patients treated for comorbid acid reflux. Although the mechanism remains unclear, the effect might pinpoint a connection between GERD and AF. To this end, it is known that both oxidants and inflammation affect initiation and maintenance of AF, and PPIs may reduce symptoms and frequency of AF episodes through their antioxidant and anti-inflammatory effects. This review focuses on the anti-AF effects of PPIs beyond their inhibition of gastric acid production.

Protective effect of piperine on electrophysiology abnormalities of left atrial myocytes induced by hydrogen peroxide in rabbits

AIMS Piperine had protective effects on oxidative stress damage of ventricular myocytes by hydrogen peroxide (H2O2). In this study we aimed to explore the protective effect of piperine on abnormalities of the cardiac action potential (AP) and several ion currents induced by hydrogen peroxide (H2O2) in single rabbit left atrial myocyte. MAIN METHODS Conventional microelectrodes were used to record action potential duration (APD), resting membrane potential (RMP) and some ion currents (ICa,L,Ito,IK1 and Ikur,ect.), before and after H2O2 administration with or without piperine. KEY FINDINGS The piperine (7 μmol/L) had no significant effect on APD, ICa,L,Ito,IK1 and Ikur and their channel dynamics. In the presence of 50 μmol/L H2O2, APD50 and APD90 shortened (P<0.01), amplitude of RMP decreased (P<0.05), the peak of ICa,L reduced significantly (P<0.05). Piperine (7 μmol/L) significantly alleviated the inhibiting effect of H2O2 on APD and ICa,L (P<0.01) and protected the changes of ICa,L dynamics induced by H2O2. The peak current of Ito was reduced significantly (P<0.05); Piperine (7 μmol/L) significantly alleviated the inhibiting effect of H2O2 on Ito (P<0.01). In addition, piperine protected the changes of Ito dynamics induced by H2O2. The peak current of IK1 and IKUr was significantly reduced (P<0.05); Piperine (7 μmol/L) alleviated the inhibiting effect of H2O2 on IK1 and IKUr significantly (P<0.01). In addition, piperine protected the changes of IKUr dynamics induced by H2O2. SIGNIFICANCE These results suggest that piperine effectively protects atrial myocytes from oxidative stress injury in atrial electrophysiology.

Establishment of a Model of Renal Impairment with Mild Renal Insufficiency Associated with Atrial Fibrillation in Canines

Background Chronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF. Methods Unilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed. Results Embolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group. Conclusions We successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model.

Impact of body mass index on the development of pocket hematoma: A retrospective study in Chinese people

Background Pocket hematoma is one of the major complications associated with cardiovascular implantable electronic devices (CIEDs) implantation. The aim of this study is to evaluate the impact of body mass index (BMI) on the occurrence of pocket hematoma after CIEDs implantation. Methods The study is a retrospective review of 972 patients receiving CIEDs implantation between 2008 and 2012 in a tertiary hospital. Results Twenty two patients (2.2%) developed severe pocket hematoma requiring re-intervention. The hematoma rate (4.6%, n = 15) of patients with a BMI of < 23 kg/m2 was significantly higher compared with that of patients with a BMI of ≥ 23 kg/m2 (1.1%, n = 7, P < 0.001). In multivariate regression analysis, a BMI < 23.0 kg/m2 may be associated with the development of severe pocket hematoma. An increase of 1.0 kg/m2 in BMI was associated with lower incidence of hematoma formation (OR: 0.84; 95% CI: 0.74-0.95; P = 0.006). Conclusion BMI < 23 kg/m2 was associated with a higher incidence of pocket hematoma, requiring re-intervention. The data support that great care must be taken when patients were with a lower BMI received CIEDs implantation.

Febuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial dysfunction

BACKGROUND Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis risk, especially in the left atrium (LA). The exact mechanism is still unclear. OBJECTIVE We assessed the effects of PAF on endothelial function, and investigated if febuxostat (FX) can attenuate endothelial dysfunction by inhibition of xanthine oxidase (XO). MATERIALS AND METHODS Eighteen male New Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or FX+pacing (FP) groups. Group P and group FP received rapid atrial pacing (RAP). Group FP was administered febuxostat (FX) for 7days before RAP. Post-procedure, blood samples were collected from the LA, right atrium (RA) and peripheral circulation. Tissues from the LA and RA were obtained. Endothelial dysfunction (thrombomodulin [TM], von Willebrand factor [VWF], asymmetric dimethylarginine [ADMA]), and indirect thrombin generation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1.2]) and oxidative stress in atrial tissue (xanthine oxidase [XO], superoxide dismutase [SOD], malondialdehyde [MDA]) were measured using an Enzyme-linked immunosorbent assay. Atrial endothelial expression of TM and VWF was measured by histology/western blotting. RESULTS AND CONCLUSIONS Endothelial dysfunction (TM, VWF, ADMA), TAT generation and oxidative stress (XO, SOD, MDA) in group P were more significant compared with that in group S (p<0.05, respectively). In group P, all of these changes occurred to a greater extent in the LA compared with those in the RA or peripheral circulation. In group FP, FX attenuated endothelial dysfunction and reduced TAT levels by inhibition of XO-mediated oxidative stress. PAF can lead to endothelial dysfunction and TAT generation by XO-mediated oxidative stress. The LA is more susceptible to these effects. FX can attenuate these changes by inhibition XO and XO-mediated oxidative stress.

Effects of allitridum on the transient outward potassium current in rats with heart failure

Objective To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). Methods The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. Results The Ito current had a significant decrease in the HF group, compared with the control group. The density of Ito in the HF group was increased after treatment of allitridum (30 µmol/L). The peak current densities of Ito were enhanced in the HF group from 6.01 ± 0.30 pA/pF to 8.41 ± 0.54 pA/pF (P < 0.01) at +50 mV after treatment with allitridum (30 µmol/L). We also determined the effect of allitridum on the gating mechanism of the Ito in the HF group. Conclusions We found that allitridum increased the Ito by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of Ito in ventricular myocytes of rats with HF.