Effect of Renal Denervation and Catheter Ablation vs Catheter Ablation Alone on Atrial Fibrillation Recurrence Among Patients With Paroxysmal Atrial Fibrillation and Hypertension: The ERADICATE-AF Randomized Clinical Trial.

Importance: Renal denervation can reduce cardiac sympathetic activity that may result in an antiarrhythmic effect on atrial fibrillation. Objective: To determine whether renal denervation when added to pulmonary vein isolation enhances long-term antiarrhythmic efficacy. Design, Setting, and Participants: The Evaluate Renal Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF) trial was an investigator-initiated, multicenter, single-blind, randomized clinical trial conducted at 5 referral centers for catheter ablation of atrial fibrillation in the Russian Federation, Poland, and Germany. A total of 302 patients with hypertension despite taking at least 1 antihypertensive medication, paroxysmal atrial fibrillation, and plans for ablation were enrolled from April 2013 to March 2018. Follow-up concluded in March 2019. Interventions: Patients were randomized to either pulmonary vein isolation alone (n = 148) or pulmonary vein isolation plus renal denervation (n = 154). Complete pulmonary vein isolation to v an end point of elimination of all pulmonary vein potentials; renal denervation using an irrigated-tip ablation catheter delivering radiofrequency energy to discrete sites in a spiral pattern from distal to proximal in both renal arteries. Main Outcomes and Measures: The primary end point was freedom from atrial fibrillation, atrial flutter, or atrial tachycardia at 12 months. Secondary end points included procedural complications within 30 days and blood pressure control at 6 and 12 months. Results: Of the 302 randomized patients (median age, 60 years [interquartile range, 55-65 years]; 182 men [60.3%]), 283 (93.7%) completed the trial. All successfully underwent their assigned procedures. Freedom from atrial fibrillation, flutter, or tachycardia at 12 months was observed in 84 of 148 (56.5%) of those undergoing pulmonary vein isolation alone and in 111 of 154 (72.1%) of those undergoing pulmonary vein isolation plus renal denervation (hazard ratio, 0.57; 95% CI, 0.38 to 0.85; P = .006). Of 5 prespecified secondary end points, 4 are reported and 3 differed between groups. Mean systolic blood pressure from baseline to 12 months decreased from 151 mm Hg to 147 mm Hg in the isolation-only group and from 150 mm Hg to 135 mm Hg in the renal denervation group (between-group difference, -13 mm Hg; 95% CI, -15 to -11 mm Hg; P < .001). Procedural complications occurred in 7 patients (4.7%) in the isolation-only group and 7 (4.5%) of the renal denervation group. Conclusions and Relevance: Among patients with paroxysmal atrial fibrillation and hypertension, renal denervation added to catheter ablation, compared with catheter ablation alone, significantly increased the likelihood of freedom from atrial fibrillation at 12 months. The lack of a formal sham-control renal denervation procedure should be considered in interpreting the results of this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01873352.

Globular chitosan prolongs the effective duration time and decreases the acute toxicity of botulinum neurotoxin after intramuscular injection in rats.

Botulinum neurotoxin (BoNT) is used for an increasing number of neurological and non-neurological indications and disorders. Since the duration of action of this neurotoxin is limited, the goal of the work was to improve the pharmacological time course of BoNT. We explored the effect of several polysaccharides on the duration of action of BoNT/A1 in rat electromyography. The formulation of BoNT/A1 containing globular chitosan increased the threshold stimulation intensity almost 2 times in 30 days after injection if compared with the baseline threshold. However, conventional linear chitosan, heparin and hyaluronic acid did not have such an effect. In addition, we compared the effectiveness of different doses of BoNT/A1 (25, 50, 75, and 100 U) with globular chitosan and compared the acute toxicity of this formulation with that of BoNT/A1 in physiological saline after intramuscular injection. The results demonstrated that the dose 25 U of BoNT/A1 with globular chitosan was both effective and safe for animals after intramuscular injection. The assessed median lethal dose (LD50) for intramuscular injection in rats was 1.4 times higher for a combination of BoNT/A1 with globular chitosan than that for a solution of BoNT/A1 in physiological saline. Thus, the results of our study have provided evidence that intramuscular injection of the formulation of BoNT/A1 (25 U) containing globular chitosan in rats is safe and significantly prolongs the effective duration time of BoNT/A1.

Outcomes of Cryoballoon Ablation in High- and Low-Volume Atrial Fibrillation Ablation Centres: A Russian Pilot Survey.

PURPOSE: The results of cryoballoon ablation (CBA) procedure have been mainly derived from studies conducted in experienced atrial fibrillation (AF) ablation centres. Here, we report on CBA efficacy and complications resulting from real practice of this procedure at both high- and low-volume centres. METHODS: Among 62 Russian centres performing AF ablation, 15 (24%) used CBA technology for pulmonary vein isolation. The centres were asked to provide a detailed description of all CBA procedures performed and complications, if encountered. RESULTS: Thirteen sites completed interviews on all CBAs in their centres (>95% of CBAs in Russia). Six sites were high-volume AF ablation (>100 AF cases/year) centres, and 7 were low-volume AF ablation. There was no statistical difference in arrhythmia-free rates between high- and low-volume centres (64.6 versus 60.8% at 6 months). Major complications developed in 1.5% of patients and were equally distributed between high- and low-volume centres. Minor procedure-related events were encountered in 8% of patients and were more prevalent in high-volume centres. Total event and vascular access site event rates were higher in women than in men. CONCLUSIONS: CBA has an acceptable efficacy profile in real practice. In less experienced AF ablation centres, the major complication rate is equal to that in high-volume centres.

Randomized trial of fish oil infusion to prevent atrial fibrillation after cardiac surgery: data from an implantable continuous cardiac monitor.

OBJECTIVE: To test the hypothesis that perioperative OMEGA-3 polyunsaturated fatty acid infusion would reduce the incidence of postoperative atrial fibrillation in patients after coronary artery bypass grafting as assessed by an implantable continuous cardiac monitor. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Thirty-nine patients with coronary artery disease who underwent surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were assigned randomly to receive either OMEGA-3 polyunsaturated fatty acids (200 mg/kg/day starting before anesthesia induction for 24 hours followed by 100 mg/kg/day for 7 days) or placebo. The primary outcome was freedom from atrial fibrillation at 2-year follow-up. Reveal(®) cardiac monitor was implanted subcutaneously in all patients. Data from the cardiac monitor were collected on the 10th day and 3, 6, 12, and 24 months postoperatively. MEASUREMENT AND MAIN RESULTS: Postoperative atrial fibrillation developed in 4 (19%) patients in the control group and in 5 (27.8%) patients in the study group at 10-day follow-up (p = 0.88). At 2-year follow-up, 5 (27.8%) patients in the control group and 6 (35.3%) patients in the study group had atrial fibrillation (p = 0.9). Atrial fibrillation duration predicted risk of cardiovascular hospitalization at the 2-year follow-up (regression coefficient estimate = 0.24, standard error 0.02, p<0.0001; R(2) = 0.74). CONCLUSIONS: Infusion of OMEGA-3 polyunsaturated fatty acids failed to prevent the occurrence of atrial fibrillation in 2 years after coronary artery bypass grafting surgery. The cumulative atrial fibrillation duration registered by the continuous cardiac monitor at the 2-year follow-up was a significant predictor of an adverse outcome.