Pharmacological Cardioversion Of Atrial Fibrillation Research Articles

Antazoline for pharmacologic cardioversion of atrial fibrillation: teaching an old drug new tricks.

Antazoline for pharmacologic cardioversion of atrial fibrillation: teaching an old drug new tricks.

Weekly journal scan: the KCa2 potassium channel as a promising target for the pharmacologic cardioversion of atrial fibrillation.

Weekly journal scan: the KCa2 potassium channel as a promising target for the pharmacologic cardioversion of atrial fibrillation.

Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Efficacy and safety of antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation depending on gender: a subanalysis of CANT II Study

Abstract Background/introduction The data on gender differences concerning antiarrhythmic drugs (AAD) applied in atrial fibrillation (AF) patients is scarce. Purpose The aim of the study was to evaluate gender differences in terms of clinical profile of AF patients, and efficacy and safety of AAD used for pharmacological cardioversion (PCV) of AF. Methods This research was a sub-analysis of retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized in terms of gender and compared in terms of clinical parameters and outcome of PCV. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion and the composite safety endpoint involved bradycardia &amp;lt;45 bpm, hypotension, syncope or death. Results The majority of patients qualified for PCV were men (n=725, 53.1%). Females were older and more symptomatic, had higher CHA2DS2-VASc score, greater prevalence of tachyarrhythmia and higher utilization of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%,P=0.588) and safety (5.2% vs. 4.6%,P=0.603) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%, P=0.664) and antazoline (77.1% vs. 80.0%, P=0.19) had similar efficacy in men and women, but propafenone had lower rate of rhythm conversion in men (64.7% vs. 79.3%, P=0.046; Figure). None of the assessed AAD differed in terms of safety profile in both genders. Logistic regression showed that, among other predictors, in women the use of amiodarone vs. other AAD (odds ratio [OR] 0.569, P=0.033), while in men administration of a amiodarone (OR 0.379, P=0.001) or propafenone (OR 0.331, P=0.002) vs. other AAD were associated with lower chance of successful rhythm conversion. Conclusions Female patients with AF share different clinical profile and similar efficacy and safety of AAD used for PCV as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further prospective investigation.

Pharmacological cardioversion of atrial fibrillation: practical considerations.

The choice between rhythm and rate control strategy represents one of the most intriguing dilemmas in the management of atrial fibrillation (AF). Although the advantage of rhythm over rate control in terms of outcome has not been equivocally proven, the initial management of patients with symptomatic episodes of AF frequently involves an attempt of early cardioversion. As electrical cardioversion (EC) is challenging in terms of fasting status and involvement of anesthesiology team, pharmacological cardioversion (PC) is usually selected as the first step towards rhythm conversion. Proper qualification for PC or EC is similar and should comprise assessment of hemodynamic status, estimation of duration of arrhythmic episode, evaluation of anticoagulation regimen, exclusion of other supraventricular arrhythmias and assessment of the chance of rhythm conversion and persistence of sinus rhythm. Finally, the choice of adequate antiarrhythmic drug (AAD) depends on the presence of structural heart disease and local experience. In patients without structural heart disease, complications occur rarely, hence traditional (propafenone, flecainide) or nonclassical Vaughan-Williams class I (antazoline) or class III (vernakalant, ibutilide or dofetilide) drugs are preferred. The presence of structural heart disease consistent with any left ventricular hypertrophy, heart failure, myocardial ischemia or valvular heart disease confines the choice of AAD to amiodarone. Given the risk of ventricular proarrhythmia of AAD, safety should always prevail over the enticing possibility of rhythm conversion. The present review aims to provide a comprehensible summary of proper qualification for PC, selection of suitable AAD and state-of-the-art periprocedural management of patients with recent-onset AF.

Discovery of a brain-sparing GIRK1/4 inhibitor for pharmacological cardioversion of atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and a significant risk factor for ischemic stroke and heart failure. Marketed anti-arrhythmic drugs can restore sinus rhythm, but with limited efficacy and significant toxicities, including potential to induce ventricular arrhythmia. Atrial-selective ion channel drugs are expected to restore and maintain sinus rhythm without risk of ventricular arrhythmia. One such atrial-selective channel target is GIRK1/4 (G-protein regulated inwardly rectifying potassium channel 1/4). Here we describe 14b, a potent GIRK1/4 inhibitor developed to cardiovert AF to sinus rhythm while minimizing central nervous system exposure – an issue with preceding GIRK1/4 clinical candidates.

Body Weight Counts—Cardioversion with Vernakalant or Ibutilide at the Emergency Department

Aim: Medication for the pharmacological cardioversion of atrial fibrillation (AF) and atrial flutter (AFL) is applied either in a fixed dose or adapted to body weight. Individual body weight might be a relevant confounder for anti-arrhythmic treatment success. Therefore, the aim of this study was to elucidate the impact of body weight on pharmacological cardioversion success, comparing weight adapted (Vernakalant) and fixed dose (Ibutilide) pharmacotherapeutic cardioversion regimes. Methods: Within this prospective observational trial, a total of 316 episodes of AF and AFL were enrolled. Patients were stratified in either a Vernakalant (n = 181) or Ibutilide (n = 135) treatment arm, based on the chosen regime, for direct comparison of treatment efficacy. Results: Conversion to sinus rhythm was achieved in 76.3% of all cases. Of note, there was no difference comparing the Vernakalant and Ibutilide treatment arms (Vernakalant 76.2% vs. Ibutilide 76.3%; p = 0.991). Within the whole study population, decreasing conversion rates with increasing body weight (adjusted odds ratio (OR) = 0.69 (0.51–0.94); p = 0.018) were observed. An independent effect of body weight within the Ibutilide treatment arm was noted, which remained stable after adjustment for potential confounders (adjusted OR = 0.55 (0.38–0.92), p = 0.022. Conclusion: Both, the Vernakalant and Ibutilide treatment arms showed comparable rates of treatment success in pharmacotherapeutic cardioversion of AF and AFL. Of utmost importance, we observed that the fixed dose of Ibutilide—as compared to the weight-adapted dose of Vernakalant—showed a reduced treatment success with increasing body weight.

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

Abstract 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 &amp;lt;48h vs others: 75.3% vs 12.0%, p&amp;lt;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 &amp;lt;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 (&amp;lt;48 hours) and in patients without the left atrium enlargement and significant renal disease. Funding Acknowledgement Type of funding sources: None. Figure 1. ROC curve analysis

Older female relatives of Covid-19 patients have an unsatisfactory perception of emergency room performance by clinical staf

Flecainide is a class I antiarrhythmic used for supraventricular tachyarrhythmias with mild adverse reactions. We present a case report in a 78-year-old male that came to the emergency department with atrial fibrillation and was subsequently treated with flecainide. During the infusion, the patient went into cardiac arrest. Cardiopulmonary resuscitation was performed until the return of spontaneous circulation was achieved after 1min and 40 seconds. Conclusion. Some trials, like The Cardiac Arrhythmia Suppression Trial (CAST), consider flecainide to be safe, but our case report, together with several other published reports brings attention to the use of flecainide in pharmacologic cardioversion of atrial fibrillation as a cause of cardiac arrest. Keywords: Older man, atrial fibrillation, emergency department, cardiac arrest, flecainide

Cardiac arrest in an older male patient treated with flecainide for atrial fibrillation

Flecainide is a class I antiarrhythmic used for supraventricular tachyarrhythmias with mild adverse reactions.We present a case report in a 78-year-old male that came to the emergency department with atrial fibrillation and was subsequently treated with flecainide. During the infusion, the patient went into cardiac arrest. Cardiopulmonary resuscitation was performed until the return of spontaneous circulation was achieved after 1 min and 40 seconds. Conclusion. Some trials, like The Cardiac Arrhythmia Suppression Trial (CAST), consider flecainide to be safe, but our case report, together with several other published reports brings attention to the use of flecainide in pharmacologic cardioversion of atrial fibrillation as a cause of cardiac arrest. Keywords: Older man, atrial fibrillation, emergency department, cardiac arrest, flecainide

Cinderella drug: an antazoline is effective in pharmacological cardioversion of atrial fibrillation - Single center experience

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Antazoline (ANT) is an old antihistaminic medication with antiarrhythmic properties. After intravenous administration ANT exerts rapid antiarrhythmic effect often resulting in conversion of persistent atrial fibrillation (AF) to sinus rhythm (SR). 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 We conducted a single center, retrospective, observational study including 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 &amp;lt;48h vs others: 75.3% vs 12.0%, p &amp;lt; 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). There were only one episode of bradycardia &amp;lt;45 bpm related to ANT administration. Conclusions Intravenous antazoline administration is effective and safe in rapid pharmacological cardioversion of paroxysmal AF, especially in the short-lasting AF (&amp;lt;48 hours) and in patients without the left atrium enlargement and significant renal disease. Abstract Figure.

Antazoline for pharmacological cardioversion of atrial fibrillation: the results of the high-volume multicenter CANT study

Abstract Background Antazoline mesylate represents a first generation antihistamine with quinidine-like antiarrhythmic properties, which allows for rapid and effective termination of atrial fibrillation (AF). Despite its widespread use in Polish emergency departments, paucity of data exists concerning safety and efficacy of antazoline in comparison to other antiarrhythmic agents. Purpose This study aimed to evaluate the pooled hitherto data on effectiveness and safety of pharmacological Cardioversion with intravenous ANTazoline (CANT Study) in short-duration atrial fibrillation. Methods This retrospective observational study was performed in 5 medical centers and comprised 1300 patients with paroxysmal or persistent AF who underwent emergent pharmacological cardioversion in the real-world setting of emergency or cardiology department. The choice of antiarrhythmic drug was left to the discretion of attending physician. The exclusion criteria involved permanent AF, other supraventricular arrhythmias, including atrial flutter, chronic antiarrhythmic therapy or preemptive electrical cardioversion. The primary endpoint was restoration of sinus rhythm up to 12 hours after antiarrhythmic drug infusion. The combined safety endpoint was bradycardia &amp;lt;45 bpm, hypotension, syncope or death. Results The mean age of study population was 67.7±11.6 years and the majority of patients were men (52.9%). The median AF episode duration was 10 (4; 24) hours, while median CHA2DS2-VASc score was 3 (2; 4) pts. Antazoline alone was administered in 45.6% of patients (n=593); amiodarone in 22.1% (n=287); propafenone in 11.5% (n=150); sotalol in 0.5% (n=6), while 20.3% (n=264) received overlapping antiarrhythmic therapy. Antazoline had the highest rhythm conversion rate (Figure), which was comparable to propafenone (78.2% vs 72.7%; RR 1.08; 95% CI:0.97–1.20; P=0.175) and superior to amiodarone (vs 66.9%; RR 1.17, 95% CI:1.07–1.28; P=0.0008) and collective amiodarone/propafenone/sotalol treatment (vs 68.6%; RR 1.14; 95% CI:1.06–1.23; P=0.0006). The rate of combined safety endpoint was comparable in patients treated with antazoline and other antiarrhythmic drugs (5.2% vs 3.9%; P=0.297). Among patients treated with antazoline, 29 exhibited bradycardia &amp;lt;45 bpm and 5 patients suffered from hypotension, but no case of syncope, nor in-hospital death was reported. Conclusion Antazoline appears to be an effective antiarrhythmic drug for cardioversion of atrial fibrillation, which is associated with low rate of relatively benign adverse events. Figure 1 Funding Acknowledgement Type of funding source: None

P1907Propensity score matched analysis of antazoline mesylate vs. amiodarone or propafenone for pharmacological cardioversion of short-duration atrial fibrillation

Abstract Background Former studies corroborated promising quinidine-like properties of antazoline mesylate facilitating rapid cardioversion atrial fibrillation (AF). Still, paucity of data exists concerning direct comparison of antazoline to other antiarrhythmic agents. Purpose The study aimed to verify the hypothesis that intravenous antazoline is non-inferior to amiodarone and/or propafenone in terms of rhythm conversion rate and safety among patients with AF. Methods After reviewing 2344 consecutive medical records with I48 code of international classification of diseases (ICD), 505 eligible patients (21.5%) with paroxysmal or persistent AF who underwent emergent pharmacological cardioversion in the real-world setting of emergency department were enrolled in retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of attending physician. Antazoline group was separately matched with corresponding amiodarone (n=218) and propafenone (n=90) cohort using propensity score matching (PSM) with nearest neighbor algorithm (ratio 1:1), adjusting for age, sex, arterial hypertension, diabetes, depressed left ventricular ejection fraction, coronary artery disease, history of stroke, AF ablation, CHA2DS2-VASc score, chronic kidney disease and duration of AF episode. The primary endpoint was restoration of sinus rhythm in the emergency department. Results The study population (mean age of 67 (59; 74) years; 53.7% females) was characterized by median AF episode duration of 10.5 (5; 24) hours. Antazoline alone was administered in 23.4% of patients (n=118); amiodarone in 47.5% (n=240); propafenone in 9.9% (n=50); while 19.2% (n=97) received ≥2 antiarrhythmic drugs. Before PSM adjustment, antazoline had comparable rhythm conversion rate to propafenone (85.6% vs. 80.0%; P=0.367) and higher than amiodarone treatment (vs. 66.7%, P=0.0002), and greater than combined amiodarone/propafenone group (68.6%; RR 1.25; 95% CI: 1.12–1.39, P=0.0001). After PSM, the use of antazoline was associated with the efficacy similar to propafenone (82.2% vs. 80.0%, RR 1.03; 95% CI: 0.84–1.25, P=0.788) and superior to amiodarone (85.3% vs. 67.0%, RR 1.27, 95% CI: 1.09–1.48, P=0.0019, number needed to treat 5.5; Figure). No major adverse actions were reported in the antazoline group. Conclusion Antazoline appears to be an efficacious and safe drug for pharmacological cardioversion of AF in real-life setting, which is at least non-inferior to existing antiarrhythmic drugs. Acknowledgement/Funding None

Intravenous antazoline, a first-generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio-venous conduction and high clinical effectiveness (AntaEP Study).

Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic properties resulting in a rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm (SR). The aim of the study was to assess the influence of antazoline on atrio-venous conduction and other electrophysiological parameters in patients undergoing AF ablation. An experimental prospective study. Patients scheduled for the first-time AF ablation, in SR and not on amiodarone were enrolled. Atrio-venous conduction assessment and invasive electrophysiological study (EPS) were performed before and after intravenous administration of 250mg of antazoline. In case of AF induction during EPS, antazoline was administered until conversion to SR or a cumulative dose of 300mg. We enrolled 14 patients: 13 (93%) men, mean age 63.4 (59.9-66.8) years, mean CHA2 DS2 -VASc score 1.6 (1.0-2.2). Antazoline was administered in a mean dose 257.1 (246.7-267.6) mg. Pulmonary vein potentials and atrial capture during pulmonary vein stimulation were present before and after the administration of antazoline. Wenckebach point and atrial conduction times did not change significantly, but atrio-ventricular node effective refractory period improved-324.7 (275.9-373.5) ms vs 284.3 (256.2-312.4) ms, P=0.02. Antazoline was effective in all 5 (100%) cases of AF induction during EPS. There were no serious adverse events. Due to the lack of influence on atrio-venous conduction and high clinical effectiveness, antazoline may be suitable for pharmacological cardioversion of AF occurring during AF ablation.

Pharmacological Cardioversion With Antazoline in Atrial Fibrillation: The Results of the CANT Study.

BackgroundAntazoline mesylate represents an antihistamine capable of rapid and safe cardioversion of atrial fibrillation, yet evidence concerning its efficacy in comparison to other medications is insufficient. The study aimed to evaluate the success rate and safety of pharmacological cardioversion of atrial fibrillation with intravenous antazoline (CANT [Cardioversion With Antazoline Mesylate] study) in the setting of the emergency department.Methods and ResultsAfter reviewing 1984 medical records, 450 eligible patients (22.7%) with short‐duration atrial fibrillation subject to pharmacological cardioversion were enrolled in a retrospective observational analysis. The choice of antiarrhythmic drug was left to the discretion of the attending physician. The primary end point was successful cardioversion in the emergency department. The safety end point comprised bradycardia <45 bpm, hypotension, syncope, or death. The study population (mean age, 65.5±11.9 years; 52.9% females) was characterized by a median atrial fibrillation episode duration of 10 hours. Antazoline, alone or in combination, was administered in 24.2% (n=109) and 40% (n=180), respectively; amiodarone was administered in 46.7% and propafenone in 9.3%, while ≥2 antiarrhythmic drugs were administered in 19.8% of patients. Antazoline had the highest success rate of pharmacological cardioversion among all drugs (85.3%), which was comparable with propafenone (78.6%; relative risk, 1.09, 95% confidence interval, 0.91–1.30; P=0.317) and higher than amiodarone treatment (66.7%; relative risk, 1.28, 95% confidence interval, 1.13–1.45; P<0.001; number needed to treat, 5.4). The rate of cardioversion with antazoline alone was higher than combined amiodarone and/or propafenone (68.1%; relative risk, 1.25; 95% confidence interval, 1.12–1.40, P=0.0001). No safety end points were reported in the antazoline group, while 5 incidents occurred in the non‐antazoline cohort (P=0.075).ConclusionsAntazoline represents an efficacious and safe method of pharmacological cardioversion in a real‐life setting.

WITHDRAWN: Pharmacological cardioversion for atrial fibrillation and flutter.

Atrial fibrillation is the commonest cardiac dysrhythmia. It is associated with significant morbidity and mortality. There are two approaches to the management of atrial fibrillation: controlling the ventricular rate or converting to sinus rhythm in the expectation that this would abolish its adverse effects. To assess the effects of pharmacological cardioversion of atrial fibrillation in adults on the annual risk of stroke, peripheral embolism, and mortality. We searched the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (2000 to 2002), EMBASE (1998 to 2002), CINAHL (1982 to 2002), Web of Science (1981 to 2002). We hand searched the following journals: Circulation (1997 to 2002), Heart (1997 to 2002), European Heart Journal (1997-2002), Journal of the American College of Cardiology (1997-2002) and selected abstracts published on the web site of the North American Society of Pacing and Electrophysiology (2001, 2002). Randomised controlled trials or controlled clinical trials of pharmacological cardioversion versus rate control in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and of any aetiology. One reviewer applied the inclusion criteria and extracted the data. Trial quality was assessed and the data were entered into RevMan. We identified two completed studies AFFIRM (n=4060) and PIAF (n=252). We found no difference in mortality between rhythm control and rate control relative risk 1.14 (95% confidence interval 1.00 to 1.31).Both studies show significantly higher rates of hospitalisation and adverse events in the rhythm control group and no difference in quality of life between the two treatment groups.In AFFIRM there was a similar incidence of ischaemic stroke, bleeding and systemic embolism in the two groups. Certain malignant dysrhythmias were significantly more likely to occur in the rhythm control group. There were similar scores of cognitive assessment.In PIAF, cardioverted patients enjoyed an improved exercise tolerance but there was no overall benefit in terms of symptom control or quality of life. There is no evidence that pharmacological cardioversion of atrial fibrillation to sinus rhythm is superior to rate control. Rhythm control is associated with more adverse effects and increased hospitalisation. It does not reduce the risk of stroke. The conclusions cannot be generalised to all people with atrial fibrillation. Most of the patients included in these studies were relatively older (>60 years) with significant cardiovascular risk factors.

Randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a single oral dose of vanoxerine for the conversion of subjects with recent onset atrial fibrillation or flutter to normal sinus rhythm: RESTORE SR

Vanoxerine is an oral, 1,4-dialkylpiperazine derivative antiarrhythmic drug being evaluated for pharmacological cardioversion of atrial fibrillation (AF). The purpose of this study was to evaluate the safety and efficacy of vanoxerine for the restoration of sinus rhythm in subjects with recent onset AF or atrial flutter (AFL). RESTORE SR (randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of a single oral dose of vanoxerine for the conversion of subjects with recent onset atrial fibrillation or flutter to normal sinus rhythm) was a prospective, multinational, randomized, double-blind, placebo-controlled trial that randomized subjects to a single oral dose of vanoxerine 400 mg or placebo (2:1 allocation). A total of 41 subjects were randomized in the study (placebo [n = 15] and vanoxerine [n = 26]). The study was terminated prematurely because of safety concerns. Overall, 61% (23 of 38) of the treated cohort had a history of AF/AFL and 66% (27 of 41) had structural heart disease (SHD). The primary efficacy end point-conversion to sinus rhythm through 24 hours-occurred in 20% (3 of 15) in the placebo arm vs 69% (18 of 26) in the vanoxerine arm (P = .0024). The mean length of stay was 4.2 ± 2.9 days in the placebo arm vs 4.7 ± 3.2 days in the vanoxerine arm (P = .6561). The primary safety end point (all-cause death, ventricular fibrillation/tachycardia requiring intervention, or torsades de pointes) occurred in no patient in the placebo arm vs 11.5% (3 of 26) in the vanoxerine arm. All 3 patients had torsades de pointes and underlying SHD. Vanoxerine is an oral, mixed ion channel blocker with IKr, INa, and L-type calcium channel activity. While oral therapy with 400 mg of vanoxerine appears effective for the termination of recent onset AF/AFL, its use was associated with a significant risk of ventricular proarrhythmia in patients with SHD.

Vernakalant as a Novel Anti-Arrhythmic Agent for Converting of Atrial Fibrillation, Molecular Mechanism, Updated Clinical Efficacy, and Future Development

The rising incidence of atrial fibrillation (AF) has stimulated researches to identify novel therapeutic options for such most common and refractory cardiac arrhythmia in clinical practice. Rhythm control strategy is shown to be associated with a lower risk of progression to permanent AF and greater clinical benefit as compared with rate control. Remarkable progress has been witnessed in rhythm control strategy particularly along with the development of mapping and ablation technology, while still should pharmacological cardioversion serve as an integrated approach for the management of AF especially in the emergency department or centers not equipped with ablation professionals. Concerns regarding the safety and efficacy of existing conventional antiarrhythmic drugs (AADs) limit their clinical use. Vernakalant, with its relatively atrial selective antiarrhythmic profile, is developed as a novel AAD for pharmacological cardioversion of AF. Its mechanisms involve potassium and sodium channels blocking effects during atrial action potential. A series of clinical trials have demonstrated the rapid, efficacious and safe effect of vernakalant over placebo or conventional AADs in terminating recent-onset AF among patients with structurally normal or minimal heart disease; but current evidence does not show a superior role of vernakalant in treating long-duration AF or atrial flutter. More evidence with respect to comparisons of vernakalant with conventional AADs as well as their synergic effects is needed. Cost-effectiveness analyses of vernakalant applied in prospective and "real world" practice remain to be assessed.

Vernakalant in an Experimental Model of Pacing-Induced Heart Failure: Lack of Proarrhythmia Despite Prolongation of Repolarization

BackgroundThe present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF). Methods and ResultsIn 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 μmol/L and 30 μmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 μmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias. ConclusionIn the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.

Vernakalant for the conversion of atrial fibrillation: the new kid on the block?

Conversion of recent onset atrial fibrillation (AF) to sinus rhythm with antiarrhythmic drugs reduces the risk of hemodynamic instability, hospitalizations, and atrial remodeling seen with persistent AF. This is the main reason for pharmacological or electrical cardioversion to be considered first line of treatment for recent onset AF. Is there a role for new antiarrhythmic drugs in the conversion of AF as the first approach to a rhythm-control strategy? Vernakalant is a novel and relativity atrial selective drug which inhibits atrial-selective K(+) currents, with only a small inhibitory effect on the rapidly activating delayed rectifier K(+) current (IKr) in the ventricle. In this brief Review, we tell the journey of vernakalant to become an attractive alternative to achieve pharmacological cardioversion of AF.