Clinical experience of new antiarrhythmic drug refralon for pharmacological cardioversion in patients with atrial fibrillation after pulmonary vein cryoablation

We present two cases of successful pharmacological cardioversion using antiarrhythmic drug refralon in patients with persistent atrial fibrillation after pulmonary vein cryoablation and ineffective electrical cardioversion. These clinical cases represent the first experience of successful use of refralon in patients who underwent cryoablation.

Cardioversion in patients with newly diagnosed non-valvular atrial fibrillation: observational study using prospectively collected registry data

Objective To investigate the clinical outcomes of patients who underwent cardioversion compared with those who did not have cardioverson in a large dataset of patients with recent onset non-valvular atrial fibrillation. Design Observational study using prospectively collected registry data (Global Anticoagulant Registry in the FIELD-AF—GARFIELD-AF). Setting 1317 participating sites in 35 countries. Participants 52 057 patients aged 18 years and older with newly diagnosed atrial fibrillation (up to six weeks’ duration) and at least one investigator determined stroke risk factor. Main outcome measures Comparisons were made between patients who received cardioversion and those who had no cardioversion at baseline, and between patients who received direct current cardioversion and those who had pharmacological cardioversion. Overlap propensity weighting with Cox proportional hazards models was used to evaluate the effect of cardioversion on clinical endpoints (all cause mortality, non-haemorrhagic stroke or systemic embolism, and major bleeding), adjusting for baseline risk and patient selection. Results 44 201 patients were included in the analysis comparing cardioversion and no cardioversion, and of these, 6595 (14.9%) underwent cardioversion at baseline. The propensity score weighted hazard ratio for all cause mortality in the cardioversion group was 0.74 (95% confidence interval 0.63 to 0.86) from baseline to one year follow-up and 0.77 (0.64 to 0.93) from one year to two year follow-up. Of the 6595 patients who had cardioversion at baseline, 299 had a follow-up cardioversion more than 48 days after enrolment. 7175 patients were assessed in the analysis comparing type of cardioversion: 2427 (33.8%) received pharmacological cardioversion and 4748 (66.2%) had direct current cardioversion. During one year follow-up, event rates (per 100 patient years) for all cause mortality in patients who received direct current and pharmacological cardioversion were 1.36 (1.13 to 1.64) and 1.70 (1.35 to 2.14), respectively. Conclusion In this large dataset of patients with recent onset non-valvular atrial fibrillation, a small proportion were treated with cardioversion. Direct current cardioversion was performed twice as often as pharmacological cardioversion, and there appeared to be no major difference in outcome events for these two cardioversion modalities. For the overall cardioversion group, after adjustments for confounders, a significantly lower risk of mortality was found in patients who received early cardioversion compared with those who did not receive early cardioversion. Study registration ClinicalTrials.gov NCT01090362 .

Pharmacological cardioversion of recent-onset atrial fibrillation in patients with chronic kidney disease: sub-analysis of the CANT study

Purpose Pharmacological cardioversion (PCV) is commonly a primary option for termination of recent-onset atrial fibrillation (AF) at the emergency departments (ED), and there are reports proving that antazoline is a noteworthy agent to restore sinus rhythm. This is a sub-analysis of the CANT study evaluating the effectiveness and safety of antazoline in patients with AF at different stages of chronic kidney disease (CKD). Methods Total n=777 patients admitted to ED for the urgent termination of AF were included into this analysis. We analysed the results concerning effectiveness and safety of PCV with special consideration of antazoline, in patients at 3 stages of CKD defined on the basis of eGFR (CKD-EPI): Group I ≥60 mL/min (n=531), Group II 45–59 mL/min (n=149), and Group III <45 mL/min (n=97). Primary end-point was the termination of AF, a restoration of a sinus rhythm and its persistence until discharge. Results Patients of group III were older and with higher prevalence of comorbidities, however, we have not found statistically significant differences in overall effectiveness of PCV in comparison with the other groups. In patients receiving amiodarone, the PCV success rate was similar in all the studied groups, but along with a renal function decline, it decreased in patients receiving antazoline (79.1 vs 35%; p<0.001), and it increased close to a significant manner in patients receiving propafenone (69.9 vs 100%; p=0.067; Figure). In patients of Group I, antazoline restored a sinus rhythm as effectively as propafenone and amiodarone, however in patients of Group III, both antazoline and amiodarone became less effective in restoring a sinus rhythm than propafenone (p=0.002 and p=0.034, respectively). The rate of safety endpoint was highest in patients of Group III (eGFR<45 mL/min), and it was significantly higher than in patients of Group I and II (p=0.008 and p=0.036, respectively). We have not observed antazoline-related adverse events in any of studied groups of patients. Conclusion This real-world registry analysis revealed a different influence of CKD on individual drug effectiveness, and while propafenone and amiodarone maintained their AF termination efficacy, antazoline became significantly less effective in restoring sinus rhythm. Its favourable safety profile has not changed. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The study received no external funding

The reinvented old player – an antazoline is effective in pharmacological cardioversion of atrial fibrillation

Introduction Antazoline (ANT) is an old antihistaminic medication with antiarrhythmic properties. After intravenous administration ANT exerts rapid antiarrhythmic effect often resulting in conversion of atrial fibrillation (AF) to sinus rhythm (SR) and is widely used in Poland for this purpose in the last years. However, published data on its effectiveness, safety and clinical utility for rapid AF termination are limited and ANT is not recognized as a cardioversion drug. Aim To assess the real-world efficacy of ANT for pharmacological cardioversion of paroxysmal and persistent non-valvular AF. Methods Our single center, retrospective, observational study included patients (pts) with history paroxysmal or persistent AF episode lasting less than 6 months, in stable cardiopulmonary condition who were qualified for elective pharmacological cardioversion with intravenous ANT. The primary end-point was the conversion of AF to SR confirmed in electrocardiography (ECG) during the 6-hours observation. Results A total of 176 pts (mean age 68.4±12.0 years, 49% male) were enrolled into the study. In 93 patients (52%) AF duration was shorter than 48 hours and median AF duration time was 24 (7–432) hours. The overall success rate of pharmacological cardioversion of AF with intravenous ANT was 45.5% (80/176 pts). The mean used dose of ANT was 250.9±65.4mg. The subgroup analysis, regarding the AF duration, suggested the effectiveness of ANT mainly in in short-lasting AF (effectiveness of antazoline based cardioversion for AF lasting <48h vs others: 75.3% vs 12.0%, p<0.001). In multivariable logistic regression model AF duration (for every 24h in AF – OR=0.97; 95% CI 0.96–0.98), the left atrium antero-posterior diameter (OR=0.92; 95% CI 0.86–0.99) and the serum creatinine level (OR=0.15; 95% CI 0.03–0.73) were identified as independent predictors of antazoline based pharmacological cardioversion effectiveness, even after adjustment for comorbidities. The ROC curves revealed that the optimal cut-off value for AF duration time predicting ANT's effectiveness was 48h (AUC=0.876; 95% CI 0.815–0.922) – Figure 1. There were only one episode of bradycardia <45 bpm related to ANT administration. Conclusions Antazoline is effective and safe in rapid pharmacological cardioversion of paroxysmal AF, especially in the short-lasting AF (<48 hours) and in patients without the left atrium enlargement and significant renal disease. FUNDunding Acknowledgement Type of funding sources: None. Figure 1. ROC curve analysis

Atrial flutter with flecainide-induced 1:1 conduction at a rate <200bpm at rest: a case report

Background Class IC antiarrhythmic drug flecainide is commonly used in the management of atrial arrhythmias and in particular atrial fibrillation (AF). Although previously reported as a potential complication, atrial flutter (AFL) with 1:1 atrioventricular conduction is rare, with only few cases reported so far, most of which related to physical activity. In all previous reported cases, 1:1 conduction resulted in ventricular rates of more than 200 b.p.m. Case Summary We report the case of a 60 year old woman, who presented to our local emergency department with palpitations related to acute onset AF. The patient developed symptomatic 1:1 AFL with a rate of 192 b.p.m., shortly after administration of intravenous flecainide, which spontaneously converted back to AF and subsequently to sinus rhythm, with further administration of amiodarone and beta blocker. Discussion The case raises awareness of this rare but potentially life threatening complication to those using flecainide for pharmacological cardioversion of AF. QRS complex widening can be seen in the context of very rapid ventricular rates, posing additional diagnostic challenge, especially with rates of less than 200 b.p.m. Prescribing an AV nodal blocking agent, such as a beta-blocker, together with flecainide reduces significantly the risk of 1:1 conduction and should always be considered.

Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

Safety and Efficacy of Ibutilide for Acute Pharmacological Cardioversion of Rheumatic Atrial Fibrillation

<b><i>Introduction:</i></b> Ibutilide is indicated for acute cardioversion of nonvalvular atrial fibrillation (AF). However, its efficacy and safety in the pharmacological cardioversion of rheumatic AF are unknown. <b><i>Methods:</i></b> Patients with mild-to-moderate rheumatic mitral valve (MV) disease with symptomatic, paroxysmal, or persistent AF were included in the analysis. Intravenous ibutilide was administered at doses tailored to body weight (0.5–2.0 mg) for over 10 min. The primary end point was efficacy, assessed as the rate of conversion of AF to sinus rhythm. The secondary end point was safety, including arrhythmic events and death within 24 h of drug initiation. <b><i>Results:</i></b> From June 2016 to October 2018, 165 patients (94 with mitral stenosis, 23 with mitral regurgitation, 11 with mixed MV disease, and 37 with MV replacement) received ibutilide (mean dose 0.90 ± 0.54 mg). Ibutilide successfully converted AF to sinus rhythm in 127/165 (76.9%) patients, with a conversion time of 7.9 ± 4.1 min. The QTc increased from 419.9 ± 15.8 to 487.5 ± 34 ms after ibutilide administration (<i>p</i> &#x3c; 0.001). The mean change in QTc after ibutilide administration (∆QTc) was 72.01 ± 36.03. There were no deaths, but 3 patients (1.8%) developed torsades de pointes (TdP) requiring defibrillation 55 ± 37 min after infusion. <b><i>Conclusion:</i></b> Ibutilide cardioverted 77% of rheumatic AF to sinus rhythm, indicating its potential as a clinically useful option for pharmacological cardioversion of rheumatic AF. TdP is a potentially serious adverse event that requires careful monitoring.