Prevention of esophageal lesions during atrial fibrillation catheter ablation using esophageal temperature monitoring: A systematic review and meta-analysis.

INTRODUCTION: The use of esophageal temperature monitoring (ETM) for the prevention of esophageal injury during atrial fibrillation (AF) ablation is often advocated. However, evidence supporting its use is scarce and controversial. We therefore aimed to review the evidence assessing the efficacy of ETM for the prevention of esophageal injury. METHODS: We performed a meta-analysis and systematic review of the available literature from inception to December 31, 2022. All studies comparing the use of ETM, versus no ETM, during radiofrequency (RF) AF ablation and which reported the incidence of endoscopically detected esophageal lesions (EDELs) were included. RESULTS: Eleven studies with a total of 1112 patients undergoing RF AF ablation were identified. Of those patients, 627 were assigned to ETM (56%). The overall incidence of EDELs was 9.8%. The use of ETM during AF ablation was associated with a non significant increase in the incidence of EDELs (12.3% with ETM, vs. 6.6 % without ETM, odds ratio, 1.44, 95%CI, 0.49, 4.22, p = .51, I2 = 72%). The use of ETM was associated with a significant increase in the energy delivered specifically on the posterior wall compared to patients without ETM (mean power difference: 5.13 Watts, 95% CI, 1.52, 8.74, p = .005). CONCLUSIONS: The use of ETM does not reduce the incidence of EDELs during RF AF ablation. The higher energy delivered on the posterior wall is likely attributable to a false sense of safety that may explain the lack of benefit of ETM. Further randomized controlled trials are needed to provide conclusive results.

Posterior pericardiotomy and the prevention of post-operative atrial fibrillation and cardiac tamponade in isolated coronary artery bypass grafting - A retrospective analysis.

BACKGROUND: Post-Operative Atrial Fibrillation (POAF) is the most frequent complication of cardiac surgery and is associated with reduced survival, increased rates of cognitive changes and cerebrovascular accidents, heart failure, renal dysfunction, infection, length of stay and hospital costs. Cardiac tamponade although less common, carries high morbidity and mortality. Shed mediastinal blood in the pericardial space is a major source of intrapericardial oxidative stress and inflammation that triggers POAF. The utilisation of a posterior pericardiotomy (PP) aims to shunt blood from pericardium into the pleural space and have a role in the prevention of POAF as well as cardiac tamponade. METHODS: 2168 patients had undergone isolated Coronary Artery Bypass Grafting at Royal Hobart Hospital from 2008 to 2022. They were divided into PP group vs. control group. Patient baseline demographics, intraoperative data and post-operative outcomes were reviewed retrospectively. RESULTS: Total incidence of new POAF and cardiac tamponade was 24% and 0.74% respectively. Primary outcome of both the incidence of POAF (20.2% vs. 26.3%, p < 0.05) and Cardiac Tamponade (0% vs. 1.1%, p < 0.05) were less in the pericardiotomy group. A subgroup analysis of patients with recent myocardial infarction showed reduced incidence of POAF in the PP group (p < 0.05). Increasing age, Body Mass Index, poor left ventricular ejection fraction (EF < 30%) and return to theatre were independent predictors of developing POAF. There were similar rates of return to theatre for bleeding however, no cases of tamponade in the pericardiotomy group. There were no complications attributable to left posterior pericardiotomy and the time added to the duration of surgery was minimal. CONCLUSION: Posterior pericardiotomy is associated with a significant reduction in the incidence of POAF and cardiac tamponade which is safe and efficient.

Stroke prevention strategies for cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Stroke is a much-feared complication of cardiac surgery, but existing literature on preventive strategies is fragmented. Hence, a systematic review and meta-analysis of stroke prevention strategies for cardiac surgery was conducted. METHODS: An electronic literature search was conducted to retrieve randomized controlled trials (RCTs) investigating perioperative interventions for cardiac surgery, with stroke as an outcome. Random-effects meta-analyses were conducted to generate risk ratios (RRs), 95% confidence intervals (95% CI), and forest plots. Descriptive analysis and synthesis of literature was conducted for interventions not amenable to meta-analysis, focusing on risks of stroke, myocardial infarction and study-defined major adverse cardiovascular events (MACE). RESULTS: Fifty-six RCTs (61 894 patients) were retrieved. Many included trials were underpowered to detect differences in stroke risk. Among pharmacological therapies, only preoperative amiodarone was shown to reduce stroke risk in one trial. Concomitant left atrial appendage closure (LAAC) significantly reduced stroke risk (RR = 0.55, 95% CI = 0.36-0.84, P = 0.006) in patients with preoperative atrial fibrillation, and there was no difference in on-pump versus off-pump coronary artery bypass grafting (CABG) (RR = 0.94, 95% CI = 0.64-1.37, P = 0.735). Much controversy exists in literature on the timing of carotid endarterectomy relative to CABG in patients with severe carotid stenosis. The use of preoperative remote ischemic preconditioning was not found to reduce rates of stroke or MACE. CONCLUSION: This review presents a comprehensive synthesis of existing interventions for stroke prevention in cardiac surgery, and identifies gaps in research which may benefit from future, large-scale RCTs. LAAC should be considered to reduce stroke incidence in patients with preoperative atrial fibrillation.

Impact of maintaining serum potassium concentration ≥ 3.6mEq/L versus ≥ 4.5mEq/L for 120 hours after isolated coronary artery bypass graft surgery on incidence of new onset atrial fibrillation: Protocol for a randomized non-inferiority trial.

BACKGROUND: Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.5mEq/L). However, there is no evidence that this strategy is efficacious. Furthermore, the approach is costly, often unpleasant for patients, and risks causing harm. We describe the protocol of a planned randomized non-inferiority trial to investigate the impact of intervening to maintain serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on incidence of new-onset AFACS after isolated elective CABG. METHODS: Patients undergoing isolated CABG at sites in the UK and Germany will be recruited, randomized 1:1 and stratified by site to protocols maintaining serum potassium at either ≥ 3.6 mEq/L or ≥ 4.5 mEq/L. Participants will not be blind to treatment allocation. The primary endpoint is AFACS, defined as an episode of atrial fibrillation, flutter or tachycardia lasting ≥ 30 seconds until hour 120 after surgery, which is both clinically detected and electrocardiographically confirmed. Assuming a 35% incidence of AFACS in the 'tight control group', and allowing for a 10% loss to follow-up, 1684 participants are required to provide 90% certainty that the upper limit of a one-sided 97.5% confidence interval (CI) will exclude a > 10% difference in favour of tight potassium control. Secondary endpoints include mortality, use of hospital resources and incidence of dysrhythmias not meeting the primary endpoint (detected using continuous heart rhythm monitoring). DISCUSSION: The Tight K Trial will assess whether a protocol to maintain serum potassium ≥ 3.6 mEq/L is non inferior to maintaining serum potassium ≥ 4.5 mEq/L in preventing new-onset AFACS after isolated CABG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816. Registered on 13 August 2019. Last update 7 January 2021.

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.

BACKGROUND: Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. METHODS: Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF. RESULTS: The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002). CONCLUSIONS: Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Inhibition of the P2X7 receptor prevents atrial proarrhythmic remodeling in experimental post-operative atrial fibrillation.

BACKGROUND: Post-operative atrial fibrillation (POAF) is a common complication in patients undergoing cardiac surgery. The purinergic receptor P2X7 (P2X7R) is involved in some cardiovascular diseases, whereas its effects on atrial fibrillation (AF) are unclear. OBJECTIVE: This study was to assess the effect of P2X7R on atrial arrhythmogenic remodeling in the rat model of sterile pericarditis (SP). METHODS: Male Sprague-Dawley (SD) rats were used to induce the SP model. Electrocardiogram, atrial electrophysiological protocol, histology, mRNA sequencing, real-time quantitative PCR, western blot, and Elisa assay were performed. RESULTS: SP significantly up-regulated P2X7R expression; increased AF susceptibility; reduced the protein expression of ion channels including Nav1.5, Cav1.2, Kv4.2, Kv4.3, and Kv1.5; caused atrial fibrosis; increased norepinephrine (NE) level in plasma; promoted the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6; increased the accumulation of immune cells (CD68- and MPO- positive cells); and activated NLRP3 inflammasome signaling pathway. P2X7R antagonist Brilliant Blue G (BBG) mitigated SP-induced alterations. The mRNA sequencing demonstrated that BBG prevented POAF mainly by regulating the immune system. In addition, another selective P2X7R antagonist A740003, and IL-1R antagonist anakinra also reduced AF inducibility in the SP model. CONCLUSIONS: P2X7R inhibition prevents SP-induced atrial proarrhythmic remodeling, which is closely associated with the improvement of inflammatory changes, ion channel expression, atrial fibrosis, and sympathetic activation. The findings point to P2X7R inhibition as a promising target for AF (particularly POAF) and perhaps other conditions.

In noncardiac thoracic surgery, low-dose colchicine did not reduce AF or myocardial injury after noncardiac surgery at 14 d.

SOURCE CITATION: Conen D, Ke Wang M, Popova E, et al; COP-AF Investigators. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial. Lancet. 2023;402:1627-1635. 37640035.

Inactivation of the NLRP3 inflammasome mediates exosome-based prevention of atrial fibrillation.

Rationale: Extracellular vesicles (EVs) from human explant-derived cells injected directly into the atria wall muscle at the time of open chest surgery reduce atrial fibrosis, atrial inflammation, and atrial fibrillation (AF) in a rat model of sterile pericarditis. Albeit a promising solution to prevent postoperative AF, the mechanism(s) underlying this effect are unknown and it is not clear if this benefit is dependent on EV dose. Methods: To determine the dose-efficacy relationship of EVs from human explant-derived cells in a rat model of sterile pericarditis. Increasing doses of EVs (106, 107, 108 or 109) or vehicle control were injected into the atria of middle-age male Sprague-Dawley rats at the time of talc application. A sham control group was included to demonstrate background inducibility. Three days after surgery, all rats underwent invasive electrophysiological testing prior to sacrifice. Results: Pericarditis increased the likelihood of inducing AF (p<0.05 vs. sham). All doses decreased the probability of inducing AF with maximal effects seen after treatment with the highest dose (109, p<0.05 vs. vehicle). Pericarditis increased atrial fibrosis while EV treatment limited the effect of pericarditis on atrial fibrosis with maximal effects seen after treatment with 108 or 109 EVs. Increasing EV dose was associated with progressive decreases in pro-inflammatory cytokine content, inflammatory cell infiltration, and oxidative stress. EVs decreased NLRP3 (NACHT, LRR, and PYD domains-containing protein-3) inflammasome activation though a direct effect on resident atrial fibroblasts and macrophages. This suppressive effect was exclusive to EVs produced by heart-derived cells as application of EVs from bone marrow or umbilical cords did not alter NLRP3 activity. Conclusions: Intramyocardial injection of incremental doses of EVs at the time of open chest surgery led to progressive reductions in atrial fibrosis and inflammatory markers. These effects combined to render atria resistant to the pro-arrhythmic effects of pericarditis which is mechanistically related to suppression of the NLRP3 inflammasome.

P2X7 receptor inhibition prevents atrial fibrillation in rodent models of depression.

AIMS: Depression, the most prevalent psychiatric disorder, is associated with the occurrence and development of atrial fibrillation (AF). P2X7 receptor (P2X7R) activation participates in the development of depression, but little attention has been given to its role in AF. This study was to investigate the effects of P2X7R on AF in depression models. METHODS AND RESULTS: Lipopolysaccharide (LPS) and chronic unpredictable stress (CUS) were carried out to induce depression in rodents. Behavioural assessments, atrial electrophysiological parameters, electrocardiogram (ECG) parameters, western blot, and histology were performed. Atrial fibrillation inducibility was increased in both LPS- and CUS-induced depression, along with the up-regulation of P2X7R in atria. CUS facilitated atrial fibrosis. CUS reduced heart rate variability (HRV) and increased the expression of TH and GAP43, representing autonomic dysfunction. Down-regulation of Nav1.5, Cav1.2, Kv1.5, Kv4.3, Cx40, and Cx43 in CUS indicated the abnormalities in ion channels. In addition, the expression levels of TLR4, P65, P-P65, NLRP3, ASC, caspase-1, and IL-1ß were elevated in depression models. Pharmacological inhibitor (Brilliant Blue G, BBG) or genetic deficiency of P2X7R significantly mitigated depressive-like behaviours; ameliorated electrophysiological deterioration and autonomic dysfunction; improved ion channel expression and atrial fibrosis; and prevented atrial NLRP3 inflammasome activation in the pathophysiological process of AF in depression models. CONCLUSION: LPS or CUS induces AF and promotes P2X7R-dependent activation of NLRP3 inflammasome, whereas pharmacological P2X7R inhibition or P2X7R genetic deficiency prevents atrial remodelling without interrupting normal atrial physiological functions. Our results point to P2X7R as an important factor in the pathology of AF in depression.

Rationale and design of the VAST-AF trial: A randomized controlled, blinded, clinical trial to evaluate transcutaneous vagal nerve stimulation for the prevention of persistent atrial fibrillation recurrence.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is linked to significant symptoms and an elevated risk of heart failure, thromboembolism and disabling stroke. Not only do patients suffer from AF and the concomitant complications, but it is a great economic burden for healthcare systems all over the world. Despite remarkable progress in the field of AF, the basic mechanisms of AF development remain unresolved. Data suggests that the (cardiac) autonomous nervous system (ANS) plays a significant role in AF. Recent studies have shown that stimulating the ANS could have a beneficial effect on paroxysmal and postoperative AF. Consequently, this therapy could provide another viable target for treating persistent AF, as well. METHODS: The VAST-AF trial is a prospective, double-blinded, randomized, and sham-controlled clinical trial. One hundred and twenty patients diagnosed with persistent AF and cardioversion in sinus rhythm (SR) will be randomly assigned to either transcutaneous vagal nerve stimulation (tVNS) or sham treatment in a 1:1 ratio. The primary objective of this study is to examine whether a daily tVNS reduces the recurrence rate of AF. Secondary endpoints include quality of life, time to first AF recurrence and ECG parameters of the ANS. Follow-up is scheduled at 30 days, 3 and 6 months. After 3 months, stimulation is withdrawn, and patients evaluated regarding a still detectable effect of tVNS. CONCLUSION: The VAST-AF trial represents the first randomized and sham-controlled study to investigate the potential benefits of transcutaneous vagal nerve stimulation on the recurrence of atrial fibrillation. Patients with persistent atrial fibrillation and successful electrical cardioversion will be assessed. A decrease in the rate of recurrence and consecutive hospitalizations could decidedly enhance the quality of life of patients and decrease healthcare expenses. Nevertheless, it does not compete with treatments such as catheter ablation, but rather serves as an additional tool in the armamentarium of the electrophysiologist.

Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention. METHODS: We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes. RESULTS: In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001]. CONCLUSION: In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required.

Effect of antecedent statin usage on conduction disturbances and arrhythmias after transcatheter aortic valve replacement.

BACKGROUND: Post-transcatheter aortic valve replacement (TAVR) conduction disturbances and atrial fibrillation (AF) are associated with markedly worse short- and long-term prognosis. Statins have multiple pleotropic effects that may be beneficial in mitigating the risk of these procedural complications as has been found for various other cardiac procedures and surgeries. METHODS: Data were retrospectively collected on consecutive patients in the Yale New Haven Health TAVR Registry who did not have a prior pacemaker, had at least 1 pre- and post-TAVR electrocardiogram, and did not have a change to their statin regimen during the index hospitalization. The primary endpoint was the composite of new pacemaker placement, new AF, and other new conduction disturbances evaluated at 7 days post-TAVR. RESULTS: Between, July 2012 and August 2019, 612 patients met inclusion criteria. Of these, 162 patients were not on antecedent statins, and 450 were (28 low-intensity, 225 moderate-intensity, and 197 high-intensity). After 1:1 propensity matching, 99 patients on moderate-/high-intensity statins were matched to 99 patients not on antecedent statins. At 7 days, there was no significant difference in the occurrence of the primary endpoint (57 % statin users vs 46 % non-statin users; p = 0.16). There was a trend toward increased conduction disturbances 7 days after TAVR in statin users (56 % vs 42 %; p = 0.07), but rates of AF (5 % vs 8 %; p = 0.39) and pacemaker placement (9 % vs 15 %; p = 0.20) were numerically lower in statin users. There was no significant difference in persistent conduction disturbances (21 % vs 18 %; p = 0.59). CONCLUSIONS: Statins do not appear to reduce the risk of post-TAVR AF or conduction abnormalities in this small retrospective study.

Exercise and Atrial Fibrillation: The Dose Makes the Poison? A Narrative Review.

"All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison" (Paracelsus, ~ 1538 AD). This well-known quote seems to aptly summarize the current understanding of the interaction between exercise and atrial fibrillation (AF). A host of data strongly suggests that regular exercise has a protective effect against developing AF. A small but well-conducted group of trials also demonstrates beneficial effects of exercise in the treatment of AF. Recently, however, potentially detrimental effects of large volumes of high-intensity exercise on the probability of developing AF have moved into the sports-cardiological focus. This effect is well documented for elite athletes; data regarding the general population is less clear. This review presents the current data regarding the protective, therapeutic and potentially risk-enhancing effects of exercise regarding AF. The authors demonstrate that the benefits are clear and strongly outweigh the potential disadvantages.

Intake reminders are effective in enhancing adherence to direct oral anticoagulants in stroke patients: a randomised cross-over trial (MAAESTRO study).

BACKGROUND: Direct oral anticoagulants (DOAC) effectively prevent recurrent ischaemic events in atrial fibrillation (AF) patients with recent stroke. However, excellent adherence to DOAC is mandatory to guarantee sufficient anticoagulation as the effect quickly subsides. AIM: To investigate the effect of intake reminders on adherence to DOAC. METHODS: MAAESTRO was a randomised, cross-over study in DOAC-treated AF patients hospitalised for ischaemic stroke. Adherence was measured by electronic monitoring for 12 months. After an observational phase, patients were randomised to obtain an intake reminder either in the first or the second half of the subsequent 6-month interventional phase. The primary outcome was 100%-timing adherence. Secondary outcomes were 100%-taking adherence, and overall timing and taking adherence. We analysed adherence outcomes using McNemar's test or mixed-effects logistic models. RESULTS: Between January 2018 and March 2022, 130 stroke patients were included, of whom 42 dropped out before randomisation. Analysis was performed with 84 patients (mean age: 76.5 years, 39.3% women). A 100%-timing adherence was observed in 10 patients who were using the reminder, and in zero patients without reminder (p = 0.002). The reminder significantly improved adherence to DOAC, with study participants having 2.7-fold increased odds to achieve an alternative threshold of 90%-timing adherence (OR 2.65; 95% CI 1.05-6.69; p = 0.039). A similar effect was observed for 90%-taking adherence (OR 3.06; 95% CI 1.20-7.80; p = 0.019). Overall timing and taking adherence increased significantly when using the reminder (OR 1.70; 95% CI 1.55-1.86, p < 0.01; and OR 1.67; 95% CI 1.52-1.84; p < 0.01). CONCLUSION: Intake reminders increased adherence to DOAC in patients with stroke attributable to atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03344146.

Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial.

BACKGROUND: Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF. METHODS: Patients scheduled for ablation were randomized to receive colchicine 0.6 mg twice daily or placebo for 10 days. The first dose of the study drug was administered within 4 hours before ablation. Atrial arrhythmia recurrence was defined as AF, atrial flutter, or atrial tachycardia >30 s on two 14-day Holters performed immediately and at 3 months following ablation. RESULTS: The modified intention-to-treat population included 199 patients (median age, 61 years; 22% female; 70% first procedure) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Antiarrhythmic drugs were prescribed at discharge in 149 (75%) patients. Colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59-1.61]; P=0.92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45-2.02]; P=0.89). Postablation chest pain consistent with pericarditis was reduced with colchicine (4% versus 15%; HR, 0.26 [95% CI, 0.09-0.77]; P=0.02) and colchicine increased diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95-11.53]; P<0.001). During a median follow-up of 1.3 years, colchicine did not reduce a composite of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation (29 versus 25 per 100 patient-years; HR, 1.18 [95% CI, 0.69-1.99]; P=0.55). CONCLUSIONS: Colchicine administered for 10 days following catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, but did reduce postablation chest pain and increase diarrhea.

Effect of Flecainide and Ibutilide Alone and in Combination to Terminate and Prevent Recurrence of Atrial Fibrillation.

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF). METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations. RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide cardioverted sustained AF in 40% and 20% of atria, respectively, but in 100% of atria when used in combination. Ibutilide prolonged atrial and ventricular effective refractory period by 15% and 8%, respectively, at a cycle length of 500 ms (P<0.05 for both). Flecainide increased the effective refractory period in atria by 27% (P<0.01) but by only 2% in the ventricles. The combination of the 2 drugs lengthened the effective refractory period by 42% in atria (P<0.01) but by only 7% (P<0.05) in the ventricles. In left ventricular wedges, ibutilide prolonged QT and Tpeak-Tend intervals by 25 and 55%, respectively (P<0.05 for both; cycle length, 2000 ms). The addition of flecainide (1.5 µmol/L) partially reversed these effects (P<0.05 for both parameters versus ibutilide alone). Torsades de Pointes score was relatively high with ibutilide alone and low with the drug combination. CONCLUSIONS: In our experimental model, a combination of flecainide and ibutilide significantly improves cardioversion and prevents the recurrence of AF compared with monotherapies with little to no risk for the development of long-QT-mediated ventricular proarrhythmia.