AimsVENTURE-AF is the first prospective randomized trial of uninterrupted rivaroxaban and vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) undergoing catheter ablation (CA).Methods and resultsTrial size was administratively set at 250, the protocol-specified target. Events were independently and blindly adjudicated. We randomly assigned 248 NVAF patients to uninterrupted rivaroxaban (20 mg once-daily) or to an uninterrupted VKA prior to CA and for 4 weeks afterwards. The primary endpoint was major bleeding events after CA. Secondary endpoints included thromboembolic events (composite of stroke, systemic embolism, myocardial infarction, and vascular death) and other bleeding or procedure-attributable events. Patients were 59.5 ± 10 years of age, 71% male, 74% paroxysmal AF, and had a CHA2DS2-VASc score of 1.6. The average total heparin dose used to manage activated clotting time (ACT) was slightly higher (13 871 vs. 10 964 units; P < 0.001) and the mean ACT level attained slightly lower (302 vs. 332 s; P < 0.001) in rivaroxaban and VKA arms, respectively. The incidence of major bleeding was low (0.4%; 1 major bleeding event). Similarly, thromboembolic events were low (0.8%; 1 ischemic stroke and 1 vascular death). All events occurred in the VKA arm and all after CA. The number of any adjudicated events (26 vs. 25), any bleeding events (21 vs. 18), and any other procedure-attributable events (5 vs. 5) were similar.ConclusionIn patients undergoing CA for AF, the use of uninterrupted oral rivaroxaban was feasible and event rates were similar to those for uninterrupted VKA therapy.Name of the Trial RegistryClinicaltrials.gov trial registration number is NCT01729871.

Mutations in KCNE1, the gene encoding the beta subunit of the slowly activating delayed rectifier potassium current (IKs) channel protein, may lead to the long QT syndrome (LQTS), a condition associated with enhanced arrhythmogenesis. Mice with homozygous deletion of the coding sequence of KCNE1 have inner ear defects strikingly similar to those seen in the corresponding human condition. The present study demonstrated and assessed the mechanism of ventricular arrhythmias in Langendorff-perfused whole heart preparations from homozygous KCNE1-/- mice compared to wild-type mice of the same age. The effects of programmed electrical stimulation with decremental pacing from the basal right ventricular epicardial surface upon electrogram waveforms recorded from the basal left ventricle were assessed and quantified using techniques of paced electrogram fractionation analysis for the first time in an experimental system. All KCNE1-/-(n = 10) but not wild-type (n = 14) mouse hearts empirically demonstrated marked pacing-induced ventricular arrhythmogenicity. This correlated with significant increases in electrogram dispersion, consistent with a wider spread in conduction velocities, in parallel with clinical findings from LQTS patients with potassium channel mutations. In contrast, introduction of 100 nM isoprenaline induced arrhythmogenicity in both KCNE1-/- (n = 7) and wild-type (n = 6) hearts during pacing. Furthermore, pretreatment with 1 muM nifedipine exerted a strong anti-arrhythmic effect in the KCNE1-/- hearts (n = 12) that persisted even in the presence of 100 nM isoprenaline (n = 6). Our findings associate KCNE1-/- with an arrhythmogenic phenotype that shows an increased dispersion of conduction velocities, and whose initiation is prevented by nifedipine, a finding that in turn may have therapeutic applications in conditions such as LQTS.

Brugada syndrome (BrS) is associated with a loss of Na + channel function and an increased incidence of rapid polymorphic ventricular tachycardia (VT) and sudden cardiac death. A programmed electrical stimulation (PES) technique assessed arrhythmic tendency in Langendorff-perfused wild-type (WT) and genetically modified (Scn5a+/−) 'loss-of-function' murine hearts in the presence and absence of flecainide and quinidine, and the extent to which Scn5a+/− hearts model the human BrS. Extra-stimuli (S2), applied to the right ventricular epicardium, followed trains of pacing stimuli (S1) at progressively reduced S1-S2 intervals.

Background— The optimal ablation strategy for persistent atrial fibrillation (AF) remains unclear. Methods and Results— This multicentre randomized study compared circumferential pulmonary vein ablation+linear ablation (control arm) versus circumferential pulmonary vein ablation+linear ablation+complex fractionated atrial electrogram (CFAE) ablation (CFAE arm) in patients with persistent AF. Circumferential pulmonary vein ablation was performed followed by roof and mitral isthmus ablation, before CFAE ablation in the CFAE arm. Ablation strategy was maintained at the first redo procedure. Sixty-five patients were recruited in each arm. The mean age was 61±10 years, 75% were men, median AF duration was 2 years, 42% had long-lasting persistent AF, 68% had associated cardiovascular disease, mean left atrial dimension was 46±6 mm, and median CHA 2 DS 2 -VASc score was 2. Ablation and procedure times were significantly longer in the CFAE arm (70±20 versus 55±17; 201±35 versus 152±45 minutes; P <0.005). After a mean follow-up of 35±5 months, single-procedural success off antiarrhythmic drugs at 12 months (CFAE: 30/65 [46%] versus control: 37/65 [57%]; P =0.29) and multiprocedural success (CFAE: 51/65 [78%] versus control: 52/65 [80%]; P =1.0) were not significantly different. At the first redo procedure, patients in the CFAE arm had a higher incidence of organized atrial tachycardia/flutter (24/33 [73%] versus 11/31 [35%]; P =0.005) and gap-related macro–re-entrant flutter (8/33[24%] versus 1/31[3%]; P =0.03). Early recurrence of atrial arrhythmia was an independent predictor of late recurrence. Conclusions— CFAE ablation did not confer incremental benefit when performed in addition to circumferential pulmonary vein ablation and linear ablation. It was associated with a higher incidence of gap-related flutter. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01711047.

No abstract

No abstract

Beta-adrenoreceptor blockade does not confer an antiarrhythmic effect and may even enhance arrhythmogenesis by increasing reentrant substrate in Scn5a+/Delta hearts while mexiletine protects against VT without modifying conduction characteristics. Together these findings permit a scheme where VT in LQT3 is initiated by triggered mechanisms but propagated by reentry.

No abstract