Yan-Fei Ruan

Over 1-year efficacy and safety of left atrial appendage occlusion versus novel oral anticoagulants for stroke prevention in atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials and observational studies

BACKGROUNDnA direct comparison of the efficacy and safety profiles of left atrial appendage occlusion (LAAO) devices and novel oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation is warranted but currently unavailable.nnnOBJECTIVEnThe aim of this study was to compare the >1-year efficacy and safety of LAAO devices and NOACs for stroke prevention in patients with atrial fibrillation.nnnMETHODSnWe performed a systematic review on randomized controlled trials (RCTs) and observational studies. RCTs were analyzed by means of a network meta-analysis method using warfarin as a bridge to compare LAAO to individual NOAC or all NOACs as a whole. Observational studies were analyzed with the meta-proportion function where pooled event rates were compared.nnnRESULTSnA total of 6 RCTs and 27 observational studies were included. A network meta-analysis of RCTs indicated that LAAO was less effective than NOACs for stroke prevention (odds ratio 0.86), but had a lower rate of hemorrhagic events during follow-up. However, a meta-proportion analysis of observational studies revealed that LAAO devices were associated with a lower rate of both thromboembolic events (1.8 events per 100 patient-years vs 2.4 events per 100 patient-years) and major bleeding events during follow-up (2.2 events per 100 patient-years vs 2.5 events per 100 patient-years) as compared with NOACs. With prolonged follow-up duration after LAAO implantation, the rate of thromboembolic events decreased (2.1, 1.8, and 1.0 events per 100 person-years for 1, 1-2, and >2 years, respectively).nnnCONCLUSIONnAlthough superiority of LAAO over NOACs was not demonstrated by RCTs in terms of stroke prevention, LAAO was found to be consistently associated with a lower rate of both thromboembolic and hemorrhagic events as compared with NOACs in observational studies.

Incidence and clinical characteristics of transient ST-T elevation during transseptal catheterization for atrial fibrillation ablation

AIMSnTransient ST-T elevation (STE) is a rare complication that occurs during transseptal catheterization. This study aims to delineate the incidence and characteristics of transient STE during transseptal catheterization for atrial fibrillation (AF) ablation.nnnMETHODS AND RESULTSnConsecutive patients who underwent fluoroscopy-guided transseptal catheterization for circumferential pulmonary vein radiofrequency ablation in Beijing An Zhen Hospital from January 2006 to January 2013 were enrolled in this study. Out of 2965 patients with a total of 3452 transseptal catheterization procedures, 13 patients (0.38%, mean age 57 ± 8, 6 female, 12 paroxysmal AF, mean left atrial diameter 35.4 ± 3.8 mm) had STE. ST-T elevation occurred after transseptal puncture in 10 patients and after pulmonary vein venography in three patients. Systolic blood pressure (129 ± 10 vs. 104 ± 20 mmHg, P < 0.001), diastolic blood pressure (78 ± 6 vs. 64 ± 11 mmHg, P < 0.001), and heart rate (83 ± 19 bpm vs. 64 ± 23 b.p.m., P = 0.022) significantly decreased when STE occurred. Eleven patients complained of chest pain, one patient complained of dizziness, and one patient had no symptoms. Patients recovered in about 4.6 min (2-10 min) with dopamine or fast saline drip. Catheter ablation of AF was completed in all the 13 patients without sequelae or other complications. Four of the 13 patients (30.8%) had recurrence of AF after a mean follow-up of 21.7 months.nnnCONCLUSIONnST-T elevation is a rare complication associated with transseptal catheterization without sequelae. Catheter ablation of AF could be safely completed in these patients.

QTc Interval Prolongation Predicts Arrhythmia Recurrence After Catheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy

BACKGROUNDnIn hypertrophic cardiomyopathy (HCM) patients complicated with atrial fibrillation (AF), catheter ablation has been recommended as a treatment option. Meanwhile, prolongation of QTc interval has been linked to an increased AF incidence in the general population and to poor outcomes in HCM patients. However, whether QTc prolongation predicts arrhythmia recurrence after AF ablation in the HCM population remains unknown.nnnMETHODS AND RESULTSnThirty-nine HCM patients undergoing primary AF ablation were enrolled. The ablation strategy included bilateral pulmonary vein isolation (PVI) for paroxysmal AF (n=27) and PVI plus left atrial roof, mitral isthmus and tricuspid isthmus linear ablations for persistent AF (n=12). Pre-procedural QTc was corrected by using the Bazetts formula. At a 14.8-month follow up, 23 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had longer QTc than non-recurrent patients (461.0±28.8 ms vs. 434.3±18.2 ms, P=0.002). QTc and left atrial diameter (LAD) were independent predictors of recurrence. The cut-off value of QTc 448 ms predicted arrhythmia recurrence with a sensitivity of 73.9% and a specificity of 81.2%. A combination of LAD and QTc (global chi-squared=13.209) was better than LAD alone (global chi-squared=6.888) or QTc alone (global chi-squared=8.977) in predicting arrhythmia recurrence after AF ablation in HCM patients.nnnCONCLUSIONSnQTc prolongation is an independent predictor of arrhythmia recurrence in HCM patients undergoing AF ablation, and might be useful for identifying those patients likely to have a better outcome following the procedure.

Long-Term Persistence of Newly Initiated Warfarin Therapy in Chinese Patients With Nonvalvular Atrial Fibrillation

Background—Despite its therapeutic efficacy, warfarin is extremely underused in Chinese patients with nonvalvular atrial fibrillation (AF). Whether the nonpersistence of warfarin treatment contributes to its underuse is not known. The aims of this study were to determine nonpersistence rates of newly started warfarin treatment in Chinese patients with nonvalvular AF and to identify the factors associated with discontinuation of the treatment. Methods and Results—We identified 1461 patients with nonvalvular AF enrolled in the Chinese Atrial Fibrillation Registry (CAFR) who newly started on warfarin therapy in the period between August 1, 2011, and June 30, 2014. During a follow-up of 426±232 days, 22.1% of patients discontinued warfarin within 3 months, 44.4% within 1 year, and 57.6% within 2 years of initiation of therapy. Patients with no or partial insurance coverage had a higher likelihood to discontinue warfarin than those with full insurance coverage (adjusted hazard ratio 1.65, 95% confidence interval [1.03–2.64]; P=0.038 and 1.66 [1.13–2.42]; P=0.009, respectively). Paroxysmal AF (1.56 [1.28–1.92]; P<0.0001), no prior stroke/transient ischemic attack/thromboembolism (1.60 [1.24–2.05]; P=0.0003), and no dyslipidemia (1.34 [1.06–1.70]; P=0.016) were also found to be independent predictors for nonpersistence of warfarin therapy. Conclusions—Nonpersistence of warfarin treatment becomes a serious problem for stroke prevention in Chinese patients with nonvalvular AF. Our findings can be used to identify patients who require closer attention or to develop better management strategy for oral anticoagulation therapy.

Catheter ablation of atrial fibrillation in patients with rheumatoid arthritis.

BACKGROUNDnRheumatoid arthritis (RA) is associated with an increased incidence of atrial fibrillation (AF). This study evaluated the safety and efficacy of catheter ablation (CA) in the treatment of AF in patients with RA, which has not been previously reported.nnnMETHODSnA total of 15 RA patients with AF who underwent CA were enrolled. For each RA patient, we selected 4 individuals (control group, 60 patients in total) who presented for AF ablation in the absence of structural heart or systemic disease and matched the RA patients with same gender, age (±2 years), type of AF, and procedure date.nnnRESULTSnPatients with RA had a significantly higher C-reactive protein level (1.81 ± 2.35 mg/dl vs. 4.14 ± 2.30 mg/dl, p=0.0320), white blood cell count (5632 ± 1200 mm(3) vs. 6361 ± 1567 mm(3), p=0.0482), and neutrophil count (3308 ± 973 mm(3) vs. 3949 ± 1461 mm(3), p=0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa) recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control group (31.7%, 19/60; p=0.579) after single procedure. In all the five patients from the RA group who developed recurrence, ATa relapsed within 90 days following index procedure (median recurrence time 18 days vs. 92 days in control group; p=0.0373). Multivariate Cox regression analysis showed that hypertension and left atrial diameter but not RA, C-reactive protein, white blood cell count, and neutrophil count were independent predictors of ATa recurrence.nnnCONCLUSIONSnCatheter ablation of AF can be safely performed in patients with RA, with a success rate comparable to that of patients without RA. RA patients tend to develop early ATa recurrence after AF ablation.

Acute administration of tumour necrosis factor-α induces spontaneous calcium release via the reactive oxygen species pathway in atrial myocytes

AimsnThe arrhythmogenic mechanisms of atrial fibrillation (AF) that are induced by acute inflammation, such as postoperative AF, are not well understood. We investigated the acute effects of tumour necrosis factor-α (TNF-α) that mimic acute inflammation on Ca2+ handling in isolated atrial myocytes and its underlying mechanisms.nnnMethods and resultsnCytosol Ca2+ handling and mitochondrial reactive oxygen species (ROS) production were studied in freshly isolated atrial myocytes of wild-type mice that were exposed to TNF-α (0.05u2009ng/mL) for 2u2009h by Ionoptix and confocal microscopy. The acute effects of TNF-α on Ca2+ handling were decreased amplitudes and prolonged decay times of Ca2+ transients in isolated atrial myocytes. A significant reduction in the sarcoplasmic reticulum (SR) Ca2+ content was detected in TNF-α treated cells, which was associated with increased spontaneous Ca2+ release events. In particular, physiological concentrations of TNF-α dramatically promoted the frequency of spontaneous Ca2+ waves and Ca2+ sparks, while the spark mass presented with reduced amplitudes and prolonged durations. The underlying mechanisms of pro-arrhythmic effects of TNF-α were further investigated. Acute exposure to TNF-α rapidly promoted mitochondrial ROS production that was correlated with the acute effect of TNF-α on Ca2+ handling, and enhanced the oxidation of calcium/calmodulin-dependent protein kinase II (CaMKII) and the phosphorylation of RyR2. However, the performance of ROS inhibitor, DL-Dithiothreitol (DTT), reversed Ca2+ handling disorders induced by TNF-α.nnnConclusionnTumour necrosis factor-α rapidly increases spontaneous Ca2+ release and promotes atrial arrhythmogenesis via the ROS pathway, which suggests that antioxidant therapy is a promising strategy for acute inflammation related AF.

Right atrial diameter and outcome of catheter ablation of atrial fibrillation

PurposeWhile AF is considered more like a left atrial (LA) disease, to what extent the right atrium contributes to the pathogenesis and ablation outcome of AF remains unclear. This study aimed to identify if right atrial diameter (RAD) could predict arrhythmia recurrence after catheter ablation of atrial fibrillation (AF).MethodsFour hundred and seventy patients with drug-resistant AF [paroxysmal AF (PAF) 196; non-PAF 274] who underwent primary catheter ablation were enrolled. Ablation strategy included complete bilateral pulmonary vein isolation (PVI) in all patients and additional linear ablation across mitral isthmus, LA roof, and tricuspid isthmus in non-PAF cases. Risk factors associated with recurrence were determined by a Cox regression model, and the predictive power was evaluated by using receiver operating characteristic curve.ResultsAfter 24.3xa0±xa018.0xa0months, 284 patients (60.6%) experienced atrial tachyarrhythmia recurrence (111 in PAF, 173 in non-PAF). RAD was moderately associated with LA diameter (rxa0=xa00.371, Pxa0<xa00.001), left ventricular ejection fraction (rxa0=xa0−0.205, Pxa0<xa00.001), and left ventricular end-diastolic diameter (rxa0=xa00.319, Pxa0<xa00.001). Multivariate Cox regression analysis demonstrated that RAD was an independent predictor for recurrence only in PAF patients with LAD ≥35xa0mm (HR 1.044, 95% CI 1.007–1.082, Pxa0=xa00.021). The RAD cutoff value of 35.5xa0mm predicts atrial tachyarrhythmia recurrence with 85.4% sensitivity and 29.2% specificity. Kaplan-Meier analysis indicated that RAD over 35.5xa0mm is associated with more recurrence after PAF ablation (log-rank Pxa0=xa00.034), comparing to those with RAD <35.5xa0mm.ConclusionsRAD predicts outcome of ablation only in patients with PAF and concurrent LA enlargement. Under this condition, RAD <35.5xa0mm is associated with a more favorable recurrence-free survival at over 2-year follow-up.

QTc interval predicts outcome of catheter ablation in paroxysmal atrial fibrillation patients with type 2 diabetes mellitus

Catheter ablation has been recommended as a treatment option for paroxysmal atrial fibrillation (PAF) patients complicated with type 2 diabetes mellitus (T2DM). PAF patients with T2DM have a higher recurrence rate after catheter ablation. Prolongation of corrected QT (QTc) interval has been linked to poor outcomes in T2DM patients. Whether the abnormal QTc interval is associated with the ablation outcome in the PAF patients with T2DM remains unknown. In this study, 134 PAF patients with T2DM undergoing primary catheter ablation were retrospectively enrolled. Pre-procedural QTc interval was corrected by using the Bazett’s formula. Cox proportional hazards models were constructed to assess the relationship between QTc interval and the recurrence of AF. After a 29.1-month follow-up period, 61 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had a longer QTc interval than non-recurrent patients (425.2±21.5 ms vs. 414.1±13.4 ms, P=0.002). Multivariate Cox regression analysis revealed that QTc interval [hazard ratio (HR)=1.026, 95% confidence interval (CI) 1.012–1.040, P=0.005] and left atrial diameter (LAD) (HR=1.125, 95% CI 1.062–1.192, P=0.003) were independent predictors of recurrent atrial tachyarrhythmia. Receiver operating characteristic analysis demonstrated that the cut-off value of QTc (418 ms) predicted arrhythmia recurrence with a sensitivity of 55.7% and a specificity of 69.9%. A combination of LAD and QTc was more effective than LAD alone (P<0.001) in predicting arrhythmia recurrence after the procedure. QTc interval could be used as an independent predictor of arrhythmia recurrence in T2DM patients undergoing AF ablation, thus providing a simple method to identify those patients who likely have a better outcome following the procedure.Catheter ablation has been recommended as a treatment option for paroxysmal atrial fibrillation (PAF) patients complicated with type 2 diabetes mellitus (T2DM). PAF patients with T2DM have a higher recurrence rate after catheter ablation. Prolongation of corrected QT (QTc) interval has been linked to poor outcomes in T2DM patients. Whether the abnormal QTc interval is associated with the ablation outcome in the PAF patients with T2DM remains unknown. In this study, 134 PAF patients with T2DM undergoing primary catheter ablation were retrospectively enrolled. Pre-procedural QTc interval was corrected by using the Bazett’s formula. Cox proportional hazards models were constructed to assess the relationship between QTc interval and the recurrence of AF. After a 29.1-month follow-up period, 61 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had a longer QTc interval than non-recurrent patients (425.2±21.5 ms vs. 414.1±13.4 ms, P=0.002). Multivariate Cox regression analysis revealed that QTc interval [hazard ratio (HR)=1.026, 95% confidence interval (CI) 1.012–1.040, P=0.005] and left atrial diameter (LAD) (HR=1.125, 95% CI 1.062–1.192, P=0.003) were independent predictors of recurrent atrial tachyarrhythmia. Receiver operating characteristic analysis demonstrated that the cut-off value of QTc (418 ms) predicted arrhythmia recurrence with a sensitivity of 55.7% and a specificity of 69.9%. A combination of LAD and QTc was more effective than LAD alone (P<0.001) in predicting arrhythmia recurrence after the procedure. QTc interval could be used as an independent predictor of arrhythmia recurrence in T2DM patients undergoing AF ablation, thus providing a simple method to identify those patients who likely have a better outcome following the procedure.

Fluconazole-induced long QT syndrome via impaired human ether-a-go-go-related gene (hERG) protein trafficking in rabbits

AimsnhERG protein trafficking deficiency has long been known in drug-induced long QT syndrome (LQTS). However, validated evidence from in vivo data kept scanty. Our goal was to investigate the proarrhythmic action of fluconazole and its underlying mechanism in an animal model.nnnMethods and resultsnTwenty female Japanese long-eared white rabbits were randomly distributed into a control group and a fluconazole group for a chronic 2-week treatment. The control group was treated with 0.5% sodium carboxymethylcellulose (CMCNa), and the fluconazole group was treated with fluconazole. Electrocardiograms (ECGs) were recorded during the experimental period. Isolated arterially perfused left ventricular wedge preparations from the rabbits were made 2 weeks after treatment, and the arrhythmia events, the transmural ECG, and action potential from both the endocardium and epicardium were recorded. The changes in hERG protein expression were measured by western blot. The fluconazole group showed a longer QT interval 1 week after treatment (P < 0.05) and a higher arrhythmia occurrence 2 weeks after treatment (P < 0.05) than the control group. The fluconazole group also showed a longer transmural dispersion of repolarization and a higher occurrence of life-threatening torsades de pointes in arterially perfused left ventricular preparations. Furthermore, western blot analysis showed that the density of mature hERG protein was lower in the fluconazole group than that in the control group.nnnConclusionnFluconazole can prolong the QT interval and possess proarrhythmic activity due to its inhibition of hERG protein trafficking in our experimental model. These findings may impact the clinical potential of fluconazole in humans.

INDUCTION OF BRUGADA SYNDROME IN THE CANINE RV WEDGE PREPARATION BY SIMULTANEOUSLY PERFUSION OF PINACIDIL, TERFENADINE AND PILSICAINIDE

background: The cellular basis for the Brugada syndrome (BS) is thought to involve an outward shift of net transmembrane current active at the end of phase 1 of the RV epicardial action potential (AP) where Ito is most prominent. In response to blockage of INa or ICa or augment of IK-ATP, IKr, IKs, or Ito, epicardium may first exhibit an accentuation of the spike-and-dome morphology of the AP, resulting in a delay in the development of the dome and accentuation of the notch, and leaving Ito unopposed during phase 1 of the action potential, leading to a predominance of outward repolarizing current at the end of phase 1. We simultaneously applied Pinacidil-a K+ channel opener, Terfenadine-a Na+ and Ca2+ channels blocker and Pilsicainide-a Na+ channel blocker to establish a model of BS in canine RV perfused wedge preparation.