Cardioversion Of Recent-onset Atrial Fibrillation Research Articles

Acute Management of Paroxysmal Atrial Fibrillation with Intravenous Flecainide plus Oral Beta-Blockers

Background: Intravenous (IV) flecainide is recommended for the pharmacological cardioversion of recent-onset atrial fibrillation (AF). The aim of this study was to study the efficacy and safety of IV flecainide, co-administered with oral b-blockers, for the cardioversion of paroxysmal AF. Methods: Single-center registry, initiated in the “Skylitseion” General Hospital of Chios in January 2020. The main inclusion criterion was IV flecainide administration plus oral b-blocker for recent-onset AF (≤48 h). The primary outcome was conversion to sinus rhythm at 2 h. Results: A total of 121 (73 males and 48 females, with mean age 61.4 years) consecutive, unselected patients who complied with the study protocol were included. A successful conversion to sinus rhythm at 2 h was achieved in 99 patients (success rate: 81.8%). The median conversion time was 11.7 min (varied from 3 to 23 min). Duration of hospitalization was significantly shorter in patients who were successfully cardioverted with IV flecainide (10.9 vs. 30.7 h, p < 0.001). No serious adverse events were recorded. Conclusion: This is one of the largest registries worldwide, evaluating the effectiveness and safety of IV flecainide co-administered with a b-blocker in the acute management of recent-onset AF. The successful conversion rate at 2 h is very high and quick with no serious adverse events.

Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis.

The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department. We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event - cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4h and 24h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s). The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision. Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4h; flecainide is definitely among the most effective for cardioversion within 24h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended.

Factors predictive of spontaneous reversion to sinus rhythm: Findings from an integrated acute atrial fibrillation pathway

Recent evidence suggests that delayed cardioversion of uncomplicated acute AF is non-inferior to early cardioversion in the Emergency Department (ED), 1 Pluymaekers N.A.H.A. Dudink E.A.M.P. Luermans J.G.L.M. et al. Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. N Engl J Med. 2019; 380: 1499-1508 Crossref PubMed Scopus (95) Google Scholar and most patients will revert spontaneously to sinus rhythm (SR) by a rate control strategy. 2 Abadie B.Q. Hansen B. Walker J. et al. Likelihood of Spontaneous Cardioversion of Atrial Fibrillation Using a Conservative Management Strategy Among Patients Presenting to the Emergency Department. Am J Cardiol. 2019; 124: 1534-1539 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar We adopted a new inter-departmental acute AF clinical pathway 3 Al-Busaidi I.S. Clare G.C. Joyce L.R. et al. Presentation, Treatment and Long-Term Outcomes of a Multidisciplinary Acute Atrial Fibrillation Pathway: A 12-Month Follow-Up Study. Heart Lung Circ. 2022; 31: 216-223 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar in 2015 which involves a ‘rate-and-wait’ strategy where patients are managed with rate control agents followed by a review in a ward-based clinic within 24-72 hours (97% attend within this time frame). Over two-thirds (71%) of pathway patients spontaneously reverted to SR by clinic review. 3 Al-Busaidi I.S. Clare G.C. Joyce L.R. et al. Presentation, Treatment and Long-Term Outcomes of a Multidisciplinary Acute Atrial Fibrillation Pathway: A 12-Month Follow-Up Study. Heart Lung Circ. 2022; 31: 216-223 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar We examined predictors of spontaneous reversion to SR at AF clinic follow-up.

Vernakalant for Cardioversion of Recent-Onset Atrial Fibrillation in the Emergency Department: The SPECTRUM Study

Introduction: Intravenous vernakalant is a therapeutic option for symptomatic, recent-onset atrial fibrillation (AF). This secondary analysis from the large SPECTRUM study assessed the safety and effectiveness of vernakalant when used in the emergency department setting (ED group) or in an inpatient hospital setting (non-ED group). Methods: This post hoc analysis of the international, observational, post-authorization SPECTRUM study included 1,289 and 720 recent-onset AF episodes in adults in the ED and non-ED groups, respectively. Safety endpoints included the evaluation of pre-defined health outcomes of interest (HOIs) and other serious adverse events (SAEs) during vernakalant treatment and during the first 24 h after the last infusion. Effectiveness endpoints comprised the rate of successful vernakalant cardioversion, the time from the start of the vernakalant infusion to cardioversion, and the length of hospital stay. Data were analysed using descriptive statistics. Results: The safety profile of vernakalant was similar in the ED and non-ED groups. In the ED group, 12 pre-defined HOIs were reported in 11 patients (0.9%); all but one occurred within 2 h after start of the first infusion. These events comprised nine significant bradycardia cases, of which one was associated with transient hypotension and three with sinus arrest, and 2 cases of atrial flutter with 1:1 conduction. Five other SAEs were reported. All patients with vernakalant-related events recovered without sequelae. No Torsade de Pointes, ventricular fibrillation, or deaths occurred. Successful cardioversion was reported in 67.8% (95% confidence interval: 65.2–70.4) and 66.4% (62.5–70.1) of episodes, with a median time to conversion of 11.0 and 10.0 min in the ED and non-ED groups, respectively. Patients had a median length of hospital stay of 7.4 h and 17.1 h in the ED and non-ED groups, respectively. Conclusion: Intravenous vernakalant was well tolerated with similar cardioversion rates in patients treated in the ED or non-ED setting and does not require admission to a coronary care unit or intensive care unit. First-line treatment with vernakalant could allow an early discharge in patients with recent-onset AF treated in the ED.

Abstract 12420: Orally Inhaled Flecainide for the Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Final Results From the Phase 2 Instant Trial

Introduction: The INSTANT trial was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset, symptomatic atrial fibrillation (AF) to sinus rhythm (SR). The initial dose-ranging stage of the trial established safety and feasibility, while showing a dose- and concentration-dependent increase in efficacy (dose range: 30-120 mg); the highest dose was selected for this evaluation. Methods: Patients with symptomatic paroxysmal AF (≤ 48 hours) self-administered 120 mg FlecIH over 8 minutes in a monitored setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. Symptoms, vital signs and adverse events were recorded. Safety analyses included all patients who received 120 mg FlecIH (N=98). Efficacy analyses were performed on a modified intention to treat population (N=81) that excluded patients with systemic flecainide present prior to dosing with study drug. Results: The population had a mean age of 60.5 years, a mean BMI of 27.0 kg/m2 and 34.7% were female. All patients reported ≥1 AF-related symptoms at baseline and 87.8% presented with AF symptoms ≤ 24 hours in duration. The conversion rate was 46.9% (95% CI: 36.4%, 57.7%), with a median time of 13.7 minutes from the start of the inhalation. A greater proportion of patients were asymptomatic or had improved symptoms following conversion of AF to SR with inhaled flecainide compared to patients whose AF did not convert (92.1% and 45.4%, respectively, p < 0.001). Two patients had CV events that were considered serious (bradycardia and atrial flutter with 1:1 AV conduction). Both CV events were transient (12 and 6 minutes, respectively), required no treatment and resolved without sequelae. Median time to discharge was 2.5 hours for patients whose AF converted to SR with inhaled flecainide and by Day 5 none had experienced AF recurrence. In contrast, 35 (81.4%) patients in the no conversion group had undergone ECV by Day 5. Conclusions: The risk-benefit of orally inhaled flecainide acetate inhalation solution for acute cardioversion of recent onset AF appears favorable and may provide a safe, effective, and convenient first-line therapeutic option for AF conversion.

Predictors of successful cardioversion of recent-onset atrial fibrillation to sinus rhythm with orally inhaled flecainide

Abstract Background Height, weight, and body mass index (BMI) are well established risk factors for atrial fibrillation (AF) but whether they are also predictors of successful pharmacological cardioversion of AF is unknown. Data from the open-label INSTANT study of flecainide acetate oral inhalation solution (FlecIH) for acute cardioversion of recent-onset symptomatic AF were examined to determine if these anthropometric measures are predictors of successful cardioversion of AF to sinus rhythm (SR) with FlecIH. Methods Logistic regression was performed on a broad array of patient and disease characteristics to identify predictors of cardioversion success at 90 minutes post-dose, and potential interactions were examined by boundary restriction analysis. Data are presented for patients receiving 120 mg FlecIH. Results Data from 81 patients (32.1% female) with a mean age of 59.8 years (range: 26.0, 84.0) were included in the analysis. This cohort had a mean weight of 87 kg (range: 57, 150), a mean height of 180 cm (range: 156, 199), and a mean BMI of 26.8 kg/m2 (range: 17.2, 37.9). A logistic regression model identified height, weight, and BMI as significant predictors of cardioversion success (p<0.01) and a boundary restriction analysis revealed a negative correlation between BMI and conversion rate across the entire dataset (see Figure 1). Clinically significant conversion rates were observed for patients with BMI values that were considered normal (BMI <25 kg/m2 = 53%; 95% CI: 36, 70), overweight (BMI ≥25 and <30 kg/m2 = 47%; 95% CI: 29, 64), and obese (BMI ≥30 and <35 kg/m2 = 43%; 95% CI: 17, 69); however, none of the severely obese patients (BMI ≥35 mg/m2) had their AF successfully converted to sinus rhythm (see Figure 2). Conclusions Successful cardioversion of recent onset AF with 120 mg FlecIH was observed in normal, overweight, and obese patients with BMI values <35 kg/m2; however, conversion rate decreases with increasing BMI. Further evaluation of FlecIH dosing in severely obese patients is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): InCarda Therapeutics

Efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation: A protocol for systematic review and meta-analysis.

Background:Atrial fibrillation (AF) is the most common tachyarrhythmia encountered in clinical practice and is associated with substantial morbidity and mortality. This study aimed to determine the efficacy and safety of vernakalant for cardioversion of recent-onset AF.Methods:A comprehensive systematic literature search will be conducted in Cochrane Library, PubMed, Web of Science, EMBASE, for randomized controlled trials (RCTs) about the vernakalant with AF. Two reviewers will independently assess the quality of the selected studies according to the Cochrane Collaboration's tool for RCTs. The bias risk of the RCT will be assessed by the Cochrane risk of bias (ROB) tool. The quality of the evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Results from these questions will be graphed and assessed using Review Manager 5.3.Results:The results of this meta-analysis will be published in a peer-reviewed journal.Conclusion:This review will evaluate the safety and efficacy of vernakalant for patients with AF, provide more recommendations for patients or researchers, and high-level evidence for clinical decision-making.

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

Abstract 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. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The study received no external funding

Efficacy of propafenone vs. amiodarone in pharmacological cardioversion of recent-onset atrial fibrillation to sinus rhythm: a pooled meta-analysis of 9 randomized controlled trials

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac dysrhythmia and is associated with substantial morbidity and mortality. It can be managed either through ventricular rate control or conversion to sinus rhythm while for the patients with recent onset of AF, the latter is the recommended choice of treatment. Purpose To determine crude rates and the likelihood of conversion to sinus rhythm from recent-onset AF and mean difference in time to do so with respect if pharmacological cardioversion with propafenone or amiodarone is utilized. Methods MEDLINE and EMBASE electronic databases were searched and after exclusion criteria were applied, a total of 94 potential studies were identified, while 9 randomized controlled trials (RCTs) were included in the meta-analysis. These RCTs were conducted from 1994 until 2019 and investigated the use of oral/intravenous propafenone vs. amiodarone to convert recent-onset AF to sinus rhythm. The main outcome measures were a) likelihood of sinus rhythm restoration and for this analysis, an odds ratio (OR) with 95% confidence interval (95% CI) was reported, and b) mean time to sinus rhythm conversion between two treatment groups and the outcome measure for this endpoint was a mean difference (MD, in minutes). In both instances, OpenMeta[Analyst] software was used to perform meta-analysis while random-effects model was used with a restricted maximum likelihood-REML correction factor. Heterogeneity between RCTs was examined by the I2 test. Results A total of 9 RCTs pooled 822 patients, 410 randomized to propafenone and 412 to amiodarone treatment. All trials reported conversion rates while 7 trials reported on the time needed to reach sinus rhythm. Of these, only trials measuring conversion time during 12 to 24 hours were considered. Seven trials monitored patients for conversion during the 24 hours, one trial up until 12 hours, and 1 trial up to 8 hours. In most trials, recent-onset AF was defined as lasting ≤48 hours, and most were designed to perform intravenous drug comparisons. On average, conversion to sinus rhythm was achieved in 76.1% cases treated with propafenone and 71.8% cases treated with amiodarone. Propafenone use was non-significantly associated with a higher likelihood of conversion to sinus rhythm compared to amiodarone (OR 1.26, 95% CI 0.825–1.912) and there was a low degree of heterogeneity observed between trials (I2=34.9%, P=0.139; Figure 1). On the other hand, treatment with propafenone was associated with a significantly shorter mean time to sinus rhythm conversion compared to amiodarone (MD −304 minutes, 95% CI −342 to −266) and there was no heterogeneity observed between included trials (I2=2.78%, P=0.440; Figure 2). Conclusion Propafenone and amiodarone are similarly efficacious in converting patients from recent-onset atrial fibrillation to sinus rhythm, however, propafenone acts significantly faster and cuts mean time to sinus rhythm for about 5 hours. Funding Acknowledgement Type of funding sources: None. Figure 1. Odds ratio for conversion to SRFigure 2. Mean difference in minutes to reach SR

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

Efficacy and Safety of flecainide p.os. in cardioversion of recent-onset atrial fibrillation

Aim: The aim of the study was to identify the level of safety and the efficacy of flecainide per o.s. in patients with recent-onset (<48 hours) AF. The management of patients with recent-onset Atrial Fibrillation (AF) presenting at emergency departments varies widely.Materials and Methods: Eighty-one eligible, consecutive patients with AF were enrolled in a prospective, randomized study. Patients were randomly allocated in two groups: patients in Group A (41 patients, 28 Men – 13 Women, mean age 64.7+ 15.67 years), received flecainide 200mg and in case of no conversion an addition of 100 mg after one hour was given. In Group B (40 patients, 26 Men – 14 Women, mean age 67.5+18.74 χρόνων) a rate control strategy was adopted. The efficacy and safety of flecainide in 45 min, 60 min, 3-6 hours, 6-12 hours, 12-24 hours and 24-36 hours were studied. The primary endpoint for efficacy was time to cardioversion. The safety of flecainide was described by registration and monitoring of side effects.Results: Successful cardioversion was achieved in 37 patients (90.24%) from Group A versus 5 patients (12.5%) from Group B (p<0.0005). Cardioversion rate was 72.97% the first three hours in patients given flecainide and most of them were discharged from the hospital. Flecainide administration (OR=2.47 – p<0.0001) and patients’ heart rate on admission (OR=1.15 – p=0.04) were associated with the success of pharmacological cardioversion in 24 hours while negative prognostic factors were patients’ age (OR=1.08 – p=0.04), duration of AF (OR=0.94 – p=0.01) and left atrium size (OR=0.87 – p=0.04). There were no reported side effects. Conclusion: In carefully selected patients presenting with recent-onset AF and without structural heart disease the use of flecainide per os has shown a significant efficacy for cardioversion and has a low incidence of adverse effects.

Frontal plane QRS-T angle in the monitoring of intravenous amiodarone infusion for pharmacological cardioversion of acute atrial fibrillation.

Intravenous amiodarone infusion is effective and widely used treatment for pharmacological cardioversion of recent-onset atrial fibrillation (Af). Although amiodarone may trigger various alterations in cardiac electrophysiology and electrocardiography (ECG), the impact of amiodarone treatment on frontal plane QRS-T angle remains unclear. Frontal plane QRS-T angle is the angle between the depolarization and repolarization axes and indicates instability in the cardiac cellular electrophysiology. Therefore, the present study aimed to investigate whether intravenous amiodarone infusion has effect on frontal plane QRS-T angle in patients with acute Af. A total of 179 patients with acute-onset Af who underwent pharmacological cardioversion with intravenous amiodarone infusion were included into the study. Patients with successful and failed pharmacological cardioversion were compared regarding pre- and post-treatment frontal plane QRS-T angle. At the end of the amiodarone infusion, sinus rhythm was restored in 112 (62.6%) patients, whereas Af was persisted in 67 (37.4%) patients. Despite the similar frontal plane QRS-T angle at baseline (59.6°±21.73°vs.60.4°±25.67°, p=0.822), patients with failed pharmacological cardioversion had significantly higher post-treatment frontal plane QRS-T angle compared to patients with successful pharmacological cardioversion (68.8°±21.71°vs.58.6°±25.15° p<0.001). Furthermore, multivariate analysis demonstrated that post-treatment increased frontal plane QRS-T angle was found to be an independent predictor of failure of pharmacological cardioversion with amiodarone infusion (OR:1.233, 95% CI:1.147-1.919, p=0.024). Amiodarone may significantly affect the frontal plane QRS-T angle. As a parameter that can be easily calculated from automated ECG recordings, frontal plane QRS-T angle may be useful in the monitoring of intravenous amiodarone treatment.

Cardioversion of recent-onset atrial fibrillation: current evidence, practical considerations, and controversies in a complex clinical scenario.

Atrial fibrillation (AF) represents the most common arrhythmia and is associated with increased morbidity and mortality generating high social costs. Due to its high prevalence, AF is usually managed not only by cardiologists but also by general practitioners or clinicians in emergency departments. The conventional classification of AF includes "recent‑onset AF" defined as an arrhythmia episode shorter than 48 hours. In patients with a definite duration of AF of less than 24 hours and a very low-risk profile (CHA2DS2VASc of 0 in men and 1 in women), the thromboembolic risk seems to be low, and the standard 4‑week anticoagulation therapy is now regarded as optional treatment. Cardioversion (electrical or pharmacological) in recent‑onset AF represents a valid rhythm control strategy. Electrical cardioversion is usually reserved for hemodynamically unstable patients and performed with biphasic waveform shocks. On the other hand, pharmacological cardioversion is preferred in hemodynamically stable patients. Several antiarrhythmic drugs have been studied so far, but some questions still remain unresolved mainly due to lack of randomized clinical trials and prospective studies. The current guidelines do not uniformly agree on which drug to use for pharmacological cardioversion, and drug preference varies widely in clinical practice. The aim of this narrative review is to sum up and critically evaluate novel evidence regarding recent‑onset AF as well as to provide some practical considerations particularly focused on rhythm control with pharmacological cardioversion.

Vernakalant for Rapid Cardioversion of Recent-Onset Atrial Fibrillation: Results from the SPECTRUM Study

AimsRapid restoration of sinus rhythm using pharmacological cardioversion is commonly indicated in patients with symptomatic recent-onset atrial fibrillation (AF). The objectives of this large, international, multicenter observational study were to determine the safety and effectiveness of intravenous (IV) vernakalant for conversion of AF to sinus rhythm in daily practice.Methods and ResultsConsenting patients with symptomatic recent-onset AF (< 7 days) treated with IV vernakalant were enrolled and followed up to 24 h after the last infusion or until discharge, in order to determine the incidence of predefined serious adverse events (SAEs) and other observed SAEs and evaluate the conversion rate within the first 90 min. Overall, 2009 treatment episodes in 1778 patients were analyzed. The age of patients was 62.3 ± 13.0 years (mean ± standard deviation). Median AF duration before treatment was 11.1 h (IQR 5.4–27.0 h). A total of 28 SAEs occurred in 26 patients including 19 predefined SAEs, i.e., sinus arrest (n = 4, 0.2%), significant bradycardia (n = 11, 0.5%), significant hypotension (n = 2, 0.1%), and atrial flutter with 1:1 conduction (n = 2, 0.1%). There were no cases of sustained ventricular arrhythmias or deaths. All patients who experienced SAEs recovered fully (n = 25) or with sequelae (n = 1). Conversion rate to sinus rhythm was 70.2%, within a median of 12 min (IQR 8.0–28.0 min).ConclusionsThis large multicenter, international observational study confirms the good safety profile and the high effectiveness of vernakalant for the rapid cardioversion of recent-onset AF in daily hospital practice.

Abstract 15742: An Open-label, Multicenter Study of Flecainide Acetate Oral Inhalation Solution Shows Acute Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm in a Dose- and Concentration-dependent Manner

Introduction: Oral and intravenous (IV) flecainide are recommended as first line therapy for pharmacological cardioversion of recent-onset atrial fibrillation (AF) in patients without known relevant structural heart disease. In the present open-label, dose-escalation study, the feasibility of using flecainide acetate inhalation solution (FlecIH) for acute conversion of recent-onset AF to sinus rhythm (SR) was evaluated. Hypothesis: We hypothesized that FlecIH quickly gives rise to plasma concentrations sufficient to rapidly restore SR in patients with recent-onset AF. Methods: Patients (n=95) with symptomatic AF (for ≤ 48 hours) were enrolled and self-administered FlecIH using a breath-actuated nebulizer (30 mg [n=10], 60 mg [n=20], 90 mg [n=21], 120 mg [n=17], and 120 mg in a formulation containing saccharin [n=27]). Blood samples were collected for flecainide plasma concentrations, electrocardiograms were obtained, cardiac rhythm with a 4-hour Holter and vital signs were monitored, and adverse events (AEs) were recorded. Patients who did not convert to SR were offered alternative treatment per the investigator’s discretion. Results: Conversion rates increased with dose and maximum plasma concentrations (C max ) of flecainide. At the highest dose, 45% of patients converted to normal SR. Patients with C max &gt; 300 ng/mL had a conversion rate of 53% whereas those with C max &lt; 200 ng/mL had a conversion rate of 33%. The median time to conversion was 3.5 min after FlecIH administration. AEs were typically mild and transient. Commonly reported AEs associated with inhalation of flecainide included: cough, throat pain, and throat irritation; at the highest dose with the formulation containing saccharin, these AEs were reported for 37%, 11%, and 4% of patients, respectively. Cardiac AEs consistent with those observed with oral and IV flecainide and considered serious were uncommon and included 2 post-conversion pauses and 1 bradycardia, and 1 atrial flutter with 1:1 atrioventricular conduction; none required treatment and all resolved without sequelae. Conclusions: FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration.

Systematic Review and Meta-analysis Appraising Efficacy and Safety of Vernakalant for Cardioversion of Recent-Onset Atrial Fibrillation.

Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent. Despite its good efficacy profile and rapid onset of action, there was still controversial evidence regarding vernakalant-related adverse events. We searched PubMed and Embase for studies that compared intravenous vernakalant with placebo or antiarrhythmic agents in patients with recent-onset atrial fibrillation (AF) lasting no more than 7 days. Efficacy and safety outcomes were the treatment-induced cardioversion rate within 90 minutes and adverse events after first exposure to study drug respectively. Nine randomized controlled trials enrolling 1296 patients were analyzed. Quantitative synthesis showed that vernakalant was superior to placebo for cardioversion of recent-onset AF within 90 minutes [49.7% vs. 6.2%, risk ratio (RR) 8.13, 95% confidence interval (CI) 5.35-12.36, P < 0.00001], and it did not achieve statistical significance in cardioversion when vernakalant was compared with ibutilide (62.4% vs. 47.3%, RR 1.32, 95% CI 1.00-1.73, P = 0.05). As for safety assessment, no significant differences were found in occurring serious adverse events (9.9% vs. 10.4%, RR 0.91, 95% CI 0.67-1.25, P = 0.57) and hypotension (5.3% vs. 3.3%, RR 1.53, 95% CI 0.86-2.73, P = 0.15) between vernakalant and comparator (either placebo, ibutilide, or amiodarone). There were trends that patients receiving vernakalant experienced more drug discontinuation (2.5% vs. 1.0%, RR 2.21, 95% CI 0.96-5.11, P = 0.06) and less any ventricular tachycardia (6.1% vs. 8.1%, RR 0.70, 95% CI 0.49-1.00, P = 0.05) than those receiving comparator, but the differences were not statistically significant. Furthermore, vernakalant was associated with a higher risk of bradycardia in comparison with comparator (6.3% vs. 1.1%, RR 4.04, 95% CI 1.67-9.75, P = 0.002). Vernakalant is effective in converting recent-onset AF to sinus rhythm rapidly, while significantly more bradycardia events are related to vernakalant in our meta-analysis.

P1080Magnetic resonance imaging after electrical cardioversion of recent-onset atrial fibrillation in anticoagulant-naive patients - a study exploring clinically silent cerebral lesions

Abstract Funding Acknowledgements Unrestricted grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, Correvio International Sárl (CH) and Selanders stiftelse Background Patients with atrial fibrillation (AF) have a high incidence of cognitive impairment, which may be related to clinically silent microembolism causing cerebral infarctions. Purpose To explore the occurrence and timing of silent brain lesions following electrical cardioversion (CV) of recent onset AF in anticoagulant-naïve patients and to further study related effects on cognitive function and biomarkers of cerebral damage, S100b. Methods Patients with AF duration &amp;lt; 48 hours were prospectively included. Brain magnetic resonance imaging (MRI) and S100b, were obtained prior, after and 7-10 days following CV. Trail making tests (TMT-A and TMT-B) and their difference, ΔΤΜΤ, were assessed prior to CV, 7-10 days and 30 days after CV. Results Forty-three patients (84% males) with mean CHA2DS2-VASc score 0.6 ± 0.7 were included. Sequential MRI, including diffusion weighted scans, showed no new brain lesions after CV. Chronic white matter hyperintensities (WMH) were present at baseline in 21/43 (49%) patients. By partitioning the study population into four major groups according to the extend of WMH (Fazekas score 0 or ≥ 1) and the presence or absence of TE risk factors (CHA2DS2-VASc score 0 or ≥ 1), the TE risk as defined by CHA2DS2-VASc score ≥ 1, was associated with a higher incidence of WMH, Pearson χ2(1,N = 43)=3.95, p = 0.047. The S100b (µg/l) levels increased significantly from baseline, (mean ± SD) 0.0472 ± 0.0182 to 0.0551 ± 0.0185 after CV, p = 0.001 and then decreased 7-10 days after CV to 0.0450 ± 0.0186, p &amp;lt; 0.001. Subgroup analysis according to the presence of at least one TE risk factor as defined by CHA2DS2-VASc score showed that statistical significance of repeated measures ANOVA was maintained; for patients with no risk factors F (2,30)=12.59, p &amp;lt; 0.001 and for patients with CHA2DS2-VASc score ≥1 F(2,36)=4.43, p &amp;lt; 0.019. Consecutive TMT scores improved successively after CV, being statistically and clinically significant for TMT-B (p &amp;lt; 0.01) and ΔΤΜΤ (p = 0.005) between 7-10 days and 30 days after CV (Reliable Change Index &amp;gt;1.96). Conclusion New brain lesions could not be detected on MRI after CV, but the high incidence of white matter hyperintensities and the transient increase in S100b may indicate transient or minor brain damage undetectable by MRI thus heightening the need to reevaluate thromboembolic risk prior to CV even in low risk patients. Abstract Figure. S100b_TMT

Pharmacologic cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis.

We sought to identify the most effective antidysrhythmic drug for pharmacologic cardioversion of recent-onset atrial fibrillation (AF). We searched MEDLINE, Embase, and Web of Science from inception to March 2019, limited to human subjects and English language. We also searched for unpublished data. We limited studies to randomized controlled trials that enrolled adult patients with AF ≤ 48 h and compared antidysrhythmic agents, placebo, or control. We determined these outcomes prior to data extraction: (i) rate of conversion to sinus rhythm within 24 h, (ii) time to cardioversion to sinus rhythm, (iii) rate of significant adverse events, and (iv) rate of thromboembolism within 30 days. We extracted data according to PRISMA-NMA and appraised selected trials using the Cochrane review handbook. The systematic review initially identified 640 studies; 30 met inclusion criteria. Twenty-one trials that randomized 2785 patients provided efficacy data for the conversion rate outcome. Bayesian network meta-analysis using a random-effects model demonstrated that ranolazine + amiodarone intravenous (IV) [odds ratio (OR) 39.8, 95% credible interval (CrI) 8.3-203.1], vernakalant (OR 22.9, 95% CrI 3.7-146.3), flecainide (OR 16.9, 95% CrI 4.1-73.3), amiodarone oral (OR 10.2, 95% CrI 3.1-36.0), ibutilide (OR 7.9, 95% CrI 1.2-52.5), amiodarone IV (OR 5.4, 95% CrI 2.1-14.6), and propafenone (OR 4.1, 95% CrI 1.7-10.5) were associated with significantly increased likelihood of conversion within 24 h when compared to placebo/control. Overall quality was low, and the network exhibited inconsistency. Probabilistic analysis ranked vernakalant and flecainide high and propafenone and amiodarone IV low. For pharmacologic cardioversion of recent-onset AF within 24 h, there is insufficient evidence to determine which treatment is superior. Vernakalant and flecainide may be relatively more efficacious agents. Propafenone and IV amiodarone may be relatively less efficacious. Further high-quality study is necessary.

16 Procainamide vs Ibutilide in the Cardioversion of Recent-Onset Atrial Fibrillation and Flutter in the Emergency Department: A Retrospective Cohort Study

Intravenous (IV) procainamide and ibutilide are two commonly used medications for the cardioversion of emergency department (ED) patients with recent-onset (<48h) atrial fibrillation (AF) and atrial flutter (AFL; either = AF/AFL) across North America. It is unclear which medication is preferable. No trials have compared these agents for this indication and North American society guidelines offer contradictory recommendations: procainamide is the drug of choice in the Canadian guideline, where ibutilide is not recommended; the converse is true in U.S. guidelines. Issues of effectiveness, safety, and ease of use may contribute to drug selection. Ibutilide carries a black-box warning for the risk for torsade de pointes (polymorphic ventricular tachycardia [VT]) and requires at least 4h of monitoring, making it riskier and more cumbersome to administer than procainamide. We compare patient selection, effectiveness, and side-effect profiles of IV procainamide and ibutilide in the treatment of ED patients with recent-onset AF/FL. This retrospective cohort study included all adults who received IV procainamide or ibutilide for recent-onset AF/FL from 01/2009 to 06/2015 in 21 community EDs within a large U.S. integrated health care delivery system. We gathered demographic and clinical variables from the electronic health record and structured manual chart review. Our effectiveness outcome was cardioversion at 90m, sustained to ED discharge. Safety outcomes were the 60m incidence of hypotension (defined as more than one systolic blood pressure <100 mmHg) and VT, at least three beats in duration. We describe patient characteristics and compare outcomes using Fisher’s exact test (two-tailed) with significance noted when p<0.05. Among 730 unique ED adults, 376 received procainamide (51.5%) and 354 (48.5%) ibutilide. The two cohorts were comparable in demographics, symptom duration, and cardiac history, but ibutilide was preferred for patients with AFL (Table). The two agents had similar 90m rates of cardioversion for AF. For AFL, however, ibutilide was more effective. Hypotension occurred in 34 procainamide recipients (9.0%), only 17 of whom (4.5%) required any treatment (IV fluids or procainamide discontinuation or both) and resolved without sequelae in all 34 cases. Non-sustained monomorphic VT was uncommon. One ibutilide patient developed torsade, which resolved with treatment. More ibutilide-recipients received observation or hospitalization (Table). ED patients selected for treatment with procainamide or ibutilide for the cardioversion of recent-onset AF/FL appear similar in demographics, cardiac history, and symptom duration. The two agents demonstrate comparable 90m effectiveness for AF, but ibutilide is more effective for AFL. Until randomized trials are conducted on patients with recent-onset AF/FL, our findings suggest that IV ibutilide may be preferable for AFL based on effectiveness, whereas procainamide may be preferable for AF based on ease of use and safety.

P4775Efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation in real-world clinical practice: the SPECTRUM post-approval safety study

Abstract Background Vernakalant is an antiarrhythmic agent designed for pharmacological conversion of recent onset of atrial fibrillation (AF) with combined action on cardiac potassium and sodium currents mainly concentrated in the atria. Purpose SPECTRUM was a post-authorisation safety study of vernakalant, conducted to collect information about real-life conditions of use and appropriate dosing, and to quantify possible medically significant risks associated with the use of vernakalant in real-world clinical practice. Methods This prospective and retrospective registry was conducted from Sep 2011 to Apr 2018 in 53 hospitals in EU countries including Austria, Denmark, Finland, Germany, Spain and Sweden. A total of 1,778 patients with 2,009 episodes of recent-onset AF received vernakalant and were followed up for 24 hours after the last infusion or until hospital discharge/end of medical encounter to obtain information on medically significant health outcomes of interest (HOIs, defined as significant hypotension, significant ventricular arrhythmia, significant atrial flutter, significant bradycardia), and serious adverse events (SAEs). Results In more than 99% of treatments, vernakalant was used in accordance to the labelled indication for conversion of AF for non-surgery (94.7%) or post-cardiac surgery patients (5.2%). Vernakalant was administered in the emergency department in 64.2% of cases, with a median stay of 7.5 hours and successfully converted 70.2% (95% CI: 68.1–72.2) of patients in the effectiveness analysis population with a median time to conversion of 11 minutes (95% CI: 8.0–27.0). A total of 19 HOIs were reported in 17 patients (0.8%, 95% CI: 0.5– .4%) with individual HOIs ranging from &lt;0.1% to 0.7% suggesting these HOIs are uncommon. Significant bradycardia was the most common HOI observed in 15 patients (0.8%, 95% CI: 0.4–1.2%), with all events occurring within the first two hours (0.8%, 95% CI: 0.4–1.2%). The incidence of significant hypotension was 0.1% (2/2,009), significant atrial flutter (with 1:1 conduction) was 0.1% (2/2,009), and significant ventricular arrhythmia (sustained ventricular tachycardia) was &lt;0.1% (1/2,009). A total of 28 SAEs, including all HOIs, were observed (1.3%, 95% CI: 0.8–1.9%); all patients fully recovered, except one who recovered with sequelae after an SAE of pericardial effusion definitely not related to vernakalant. There were no cases of torsades de pointes, ventricular fibrillation, or deaths reported in the SPECTRUM study. Conclusion(s) SPECTRUM is, to our knowledge, the largest drug registry conducted on the cardioversion of recent onset AF. The cumulative data from 2,009 vernakalant treatment episodes demonstrate an incidence of HOIs and SAEs similar or lower to what has been reported in earlier vernakalant IV clinical trials. The observed conversion rate was higher than reported in pivotal trials supporting vernakalant's efficacy and allowing early discharge. Acknowledgement/Funding Study funded by Correvio International Sarl, Geneva, Switzerland