Pharmacological Conversion Of Atrial Fibrillation Research Articles

Safety and Effectiveness of Pharmacologic Conversion of Atrial Fibrillation and Flutter: Results of Multicenter Trial. Part II: Assessment of Safety

Aim.We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 micrograms/kg) intravenously.Results.Conversion of AFib and AFl into sinus rhythm was achieved in 53,6% after administration of 10 mcg/kg dose, in 73% after administration of 20 mcg/kg dose and in 91,6% after administration of Refralon in dose up to 30 mcg/kg. No mortality and no major adverse cardiac events registered in our study. Asystole >3.0 sec observed in 5% (35 of 727) of patients): in 5% (24 of 451) of patients enrolled in primary center and in 4% (11 of 276) of patients enrolled in other hospitals; 95% confidence interval (CI) [-0.09; 0.113]. Asystole> 5.0 s observed in 1.7% of patients who further required non-urgent implantation of a permanent pacemaker due to manifestations of sinus node dysfunction. Cardiac conduction disturbances (exclusively sinus bradycardia) were registered in 7% (53 of 727) patients: in 8% (37 of 451) of patients enrolled in primary center and in 6% (17 of 276) of patients enrolled in other hospitals; 95% CI: [-0.1; 0.15]. Only 0.14% of patients had symptomatic sinus bradycardia that resolved after atropine injection. Ventricular arrhythmias (exclusively Torsade de pointes tachycardia in excessive QT interval prolongation) were registered in 1.7% (12 of 727) patients: in 2% (9 of 451) of patients in primary center and in 1% (3 of 276) of patients of other hospitals; 95% CI: [-0.06; 0.08]. QTc interval prolongation to values >500 ms documented in 19% (138 of 727) of patients: in 21% (95 of 451) of patients in primary center and in 16% (43 of 276) of patients in other hospitals; 95% CI: [-0.13; 0.24].Conclusion:In post-registration multicenter trial Refralon demonstrated good safety profile in conversion of AFib and AFl. Potential risk of TdP tachycardia mandates precautions with the use of the drug. In other hospitals Refralon did not demonstrate lower safety than in primary medical center.

Early pharmacologic conversion of atrial fibrillation after off-pump coronary artery bypass grafting.

BackgroundThe aim of this study was to evaluate the efficacy of early amiodarone-based pharmacological cardioversion for postoperative atrial fibrillation (POAF) following off-pump coronary bypass grafting (OPCAB).MethodsA total of 507 patients who underwent OPCAB between 2015 and 2017 were categorized into POAF (n=94) and no-POAF (n=413) groups. Patients in the POAF group were treated according to the following institutional protocol: 150 mg loading dose of intravenous amiodarone, followed by oral administration with sequential maintenance doses at 600, 400, and 200 mg per day. If sinus rhythm was restored before discharge, patients were discharged without amiodarone or anticoagulants, except for dual antiplatelets.ResultsBefore discharge at index hospitalization, 97.8% of POAF patients had restored sinus rhythm. Independent risk factors for POAF were age, unstable angina, prior percutaneous transluminal coronary angioplasty, and left atrial diameter. The mean follow-up duration was 41.1±12.8 months. Freedom from overall mortality and composite events, including mortality, major bleeding requiring admission and cerebrovascular events, were similar between the 2 groups. Results were consistent after propensity-score matching.ConclusionsAmiodarone-based rapid pharmacological cardioversion of POAF resulted in a high sinus rhythm conversion rate (97.9%). Rate of late adverse cardiovascular events including stroke, were low even without anticoagulation. As optimal treatment and anticoagulation guidelines for POAF after OPCAB have not yet been established, amiodarone-based treatment protocols may be considered as a useful option.

Safety and Effectiveness of Pharmacologic Conversion of Atrial Fibrillation and Flutter: Results of Multicenter Trial. Part I: Study Rationale, Design and Assessment of Effectiveness

Aim.We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 mcg/kg) intravenously. Primary endpoints: restoration of sinus rhythm (SR) within 24 hours after the start of infusion of the study drug in a total dose of up to 30 pg / kg; registration of SR on an electrocardiogram (ECG) 24 hours after the start of the study drug infusion. Secondary endpoints: restoration of SR after infusion of the study drug at a dose of 10 pg / kg; restoration of SR after infusion of the studied drug in a total dose of up to 20 pg / kg; no recurrence of AFib/AFl after restoration of AFl within 24 hours of observation after the start of the study drug infusion.Results.Conversion to SR was achieved in 53,6% (391 of 727) after administration of 10 mcg/kg dose, in 73% (531 of 727) after administration of 20 mcg/kg dose and in 91,6% (666 of 727) after administration in dose up to 30 mcg/kg. SR was restored in 89% (402 of 451) of patients in primary center, and in 96% (264 of 276) of patients in other hospitals; 95% confidence interval (CI): (-0,1;-0,03). SR preserved 24 hours after conversion in 98% (650 of 666) successfully converted patients. In primary center SR preserved in 97% (390 of 402) successfully converted patients. In other hospitals - in 98,5% (260 of 264) successfully converted patients. 95 CI: (-0,09;0,06).Conclusion:In post-registration multicenter trial Refralon demonstrated high effectiveness in conversion of AFib and AFl to SR. In other hospitals Refralon did not demonstrate lower effectiveness than in primary medical center.

Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis

Objectives: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. Methods: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. Results: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p < 0.001). Sotalol was not significantly different from class IA antiarrhythmic drugs. Similarly, sotalol was not different from class IC antiarrhythmic drugs or amiodarone in terms of conversion efficacy. In one study, sotalol was less effective than high-dose ibutilide (2 mg), with a relative success of 0.248 (95% CI 0.128-0.481, p < 0.001). Ibutilide caused more proarrhythmia. Conclusions: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF.

Acute conversion of persistent atrial fibrillation during dofetilide loading does not predict long-term atrial fibrillation-free survival.

Pharmacologic conversion of atrial fibrillation and flutter (AF/AFl) is common with dofetilide. We determined whether pharmacologic conversion with dofetilide predicts long-term arrhythmia-free survival. We retrospectively studied a cohort of 264 consecutive patients who initiated dofetilide during persistent AF/AFl between 2008 and 2013. Patients were excluded if dofetilide was discontinued prior to five doses or electrical cardioversion was performed prior to four doses. Incidence of and characteristics associated with pharmacologic conversion were determined. Patients were followed for long-term AF/AFl recurrence. Predictors of recurrence were identified using multivariate Cox modeling. Of 205 patients meeting study criteria, 92 (44.9%) converted to sinus rhythm during dofetilide loading. Female gender, history of AFl, greater number of prior catheter ablations, shorter duration of current AF/AFl, and presentation in AFl were all associated with acute pharmacologic conversion (p = 0.001, 0.05, 0.001, 0.003, and 0.003, respectively). In multivariate modeling, longer time since first AF/AFl diagnosis (hazard ratio (HR) = 1.07 per 1-year increase, 95% confidence interval (CI) 1.03-1.10, p < 0.001), longer duration of current AF/AFl episode (HR = 1.01 per 1-month increase, 95% CI 1.00-1.01, p = 0.003) and greater number of failed antiarrhythmic drugs (HR = 1.43 per one drug increase, 95% CI 1.20-1.70, p < 0.001) were independently associated with shorter time to AF/AFl recurrence. Pharmacologic conversion was not significantly associated with time to AF/AFl recurrence (HR = 0.79, 95% CI 0.57-1.10, p = 0.2). Acute pharmacologic conversion of persistent AF/AFl to sinus rhythm frequently occurs during dofetilide loading. Nevertheless, acute pharmacologic conversion does not predict long-term arrhythmia control, which was moderate at best.

Electrophysiological and Hemodynamic Effects of Vernakalant and Flecainide During Cardiac Resynchronization in Dyssynchronous Canine Hearts

Patients with heart failure and left bundle branch block (LBBB) are frequently treated with biventricular pacing (BiVP). Approximately one-third of them suffer from atrial fibrillation. Pharmacological conversion of atrial fibrillation is performed with drugs that slow ventricular conduction, but the effects of these drugs on the benefit of BiVP are poorly understood. Experiments were performed in dogs with chronic LBBB, investigating the effects of Vernakalant and Flecainide (n = 6 each) on hemodynamics and electrophysiology during epicardial (EPI) and endocardial BiVP. The degree of dyssynchrony and conduction slowing was quantified using QRS width and EPI electrical mapping. Compared with LBBB, EPI and endocardial BiVP reduced QRS duration by 7% ± 9% (P < 0.05 compared with LBBB) and 20% ± 13% (P < 0.05 compared with LBBB, P < 0.05 between modes), respectively. During BiVP, the administration of Vernakalant and Flecainide increased QRS duration by 20% ± 14% (P < 0.05 compared with predrug BiVP) and 34% ± 10% (P < 0.05 compared with predrug BiVP, P < 0.05 between drugs). left ventricular (LV) dP/dtmax decreased by 16% ± 8% (P < 0.05 compared with predrug BiVP) during Vernakalant and by 14% ± 15% (P < 0.05 compared with predrug BiVP) during Flecainide. The drugs did not affect the relative changes in QRS width and LV dP/dtmax induced by BiVP. Vernakalant and Flecainide decrease contractility, slow myocardial conduction velocity, and increase activation time. The electrical and hemodynamic benefits of BiVP are not altered by the drugs.

Usefulness of Pharmacologic Conversion of Atrial Fibrillation During Dofetilide Loading Without the Need for Electrical Cardioversion to Predict Durable Response to Therapy

Conversion of persistent atrial fibrillation (AF) to sinus rhythm is frequently seen during the 3-day in-hospital loading period required during dofetilide initiation, but it is not known whether pharmacologic conversion (PC) without the need for electrical cardioversion (EC) is a predictor of long-term maintenance of sinus rhythm during continued therapy with dofetilide. We sought to test the hypothesis that PC predicts durable maintenance of sinus rhythm and determine additional predictors of long-term maintenance of sinus rhythm on dofetilide. We retrospectively reviewed all elective inpatient admissions for dofetilide loading from 2003 to 2011 at the University of Virginia. A multivariate Cox proportional hazards model was used to assess predictors of maintenance of sinus rhythm after in-hospital dofetilide loading. In all, 101 patients with a current duration of AF lasting for a median of 1.86 months (interquartile range 0.47 to 6.03) were included in the analysis. Forty-seven patients were in the PC group, whereas 54 patients were in the EC group. Patients in the PC group remained longer in sinus rhythm compared with the patients in the EC group (log-rank p = 0.032). The seventy-fifth percentile for the current episode duration in the PC group was 5.77 months, indicating that even long-standing persistent AF frequently converted pharmacologically. Hypertension and a longer duration of the current AF episode were also predictors of recurrence in the multivariate model. In conclusion, PC during in-hospital dofetilide loading is an important predictor of durable response even in long-standing persistent patients, which has important public health implications for choice of therapy.

Treating arrhythmias: an expert opinion

Introduction: Significant progress has recently been made in the pharmacological treatment of arrhythmias. This concerns mainly atrial fibrillation, which affects millions of patients.Areas covered: This review covers recent, clinically relevant developments in arrhythmia treatment, especially with regard to novel agents for the management of atrial fibrillation: dronedarone for rhythm control, vernakalant for pharmacological conversion, and advances in antithrombotic treatment. The field of pharmacological treatment of ventricular arrhythmias is also briefly discussed. Relevant papers were identified by an extensive Pubmed search using appropriate keywords.Expert opinion: Dronedarone has been proposed as one of the first-choice antiarrhythmic drugs for almost all categories of patients with atrial fibrillation. However, its effectiveness in prevention of arrhythmia recurrences is less than that of amiodarone. Administration to patients with severe heart failure is associated with increased mortality and should be avoided. There are also very recent reports over rare but severe cases of hepatic injury in patients treated with dronedarone, including two cases of acute liver failure leading to liver transplant. Intravenous vernakalant is effective for the rapid pharmacological conversion of atrial fibrillation. Dabigatran, an oral direct thrombin inhibitor, has been shown to be effective in stroke reduction without increase in bleeding rates; additionally, no monitoring of antithrombotic effectiveness is needed. Rivaroxaban, an oral direct factor Xa inhibitor, has also shown promising results. These developments in the pharmacological treatment of arrhythmia will presumably affect clinical decision making.

Pharmacologic Conversion of Atrial Fibrillation and Atrial Flutter.

Atrial fibrillation and atrial flutter are common arrhythmias in everyday clinical settings. Pharmacologic cardioversion (CV) is a simple and widely used strategy for the treatment of these arrhythmias, and many drugs are currently available. The choice of drug is strongly influenced by the time elapsed from atrial fibrillation onset and by a patient's clinical subset. Electrical direct-current CV is the treatment of choice in long-lasting forms; nevertheless, some agents also show efficacy in this setting. In addition, promising results come from studies on the efficacy and safety of new antiarrhythmic drugs and from therapeutic approaches that reduce the need for hospitalization and improve quality of life.

Enhanced efficacy with MgSO4 due to an additive, alternative, or dual mode of action?

Pharmacological conversion of atrial fibrillation–atrial flutter (AF–AFl) is still an important therapeutic modality in daily patient care. Frequently used drugs are the class III anti-arrhythmics dofetilide, sotalol, and ibutilide. By blocking (specific) potassium currents, they will prolong the duration of the action potential (APD) providing less space for re-entry to manoeuvre. Their effectiveness is still not optimal and is also hampered by their pro-arrhythmic risk due to dose-dependent lengthening of the (ventricular) repolarization times. Their use is therefore restricted, including hospitalizations when therapy is started, as was the case in this single site (Hartford Hospital) retrospective investigation (2000–08) about the effectiveness of dofetilide to acutely convert AF–AFl.1 To protect their patients for dofetilide-induced torsade de pointes (TdP) arrhythmias, some ( n = 50) from the 160 eligible patients with AF–AFl received adjunctive magnesium sulfate (Mg). The evaluation demonstrated that a single or repeated bolus of Mg (mean ± 3 g MgSO4) did not only protect for drug-induced adverse effects (0/50 vs. 1/110 TdP occurrences), but also improved the efficacy of dofetilide to suppress/prevent AF–AFl: 38% without vs. 50% with Mg, P < 0.05. This important improvement with this combination (doubling of the odds), which was recently also shown for ibutilide and Mg by … *Corresponding author. Tel: +31 30 2538900, Fax: +31 30 2539036, Email: m.a.vos{at}umcutrecht.nl

Letter by Reiffel Regarding Article, “Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm”

HomeCirculationVol. 119, No. 3Letter by Reiffel Regarding Article, “Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Reiffel Regarding Article, “Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm” James A. Reiffel James A. ReiffelJames A. Reiffel Columbia University College of Physicians & Surgeons, The New York-Presbyterian Hospital, New York, NY Search for more papers by this author Originally published27 Jan 2009https://doi.org/10.1161/CIRCULATIONAHA.108.806273Circulation. 2009;119:e17To the Editor:I read with great interest the Special Report by Drs William Hiatt, Michael Lincoff, and Robert Harrington1 on acute pharmacological conversion of atrial fibrillation (AF) to sinus rhythm. Their report provides the reader some fascinating insight into the deliberations of the Cardiovascular and Renal Drugs Advisory Committee, as well as a glimpse into the authors’ personal opinions as to the value (or lack thereof) of pharmacological cardioversion. In my opinion, although their thoughtful deliberations raised some significant and valid issues for consideration, several important points related to this topic were presented in a biased manner or not even considered. (1) The success of cardioversion is time dependent, especially for drug conversion, and “watchful waiting,” as was discussed several times in the report, would have been detrimental to success in the trials (especially because many of the patients were not treated on the first day of their AF) and misleading to practitioners, who must ultimately consider using such therapy if/when available. A no-treatment run-in phase, as suggested by the authors, clearly would also have been adverse to successful results. Moreover, in clinical practice in which the drugs being considered would be used, waiting for spontaneous conversion for >24 hours is generally not practiced unless the patient is both anticoagulated and tolerating their AF well. (2) The risk of thromboembolism is also time dependent after the onset of AF, and watchful waiting may increase its risk or increase the need for initiation of anticoagulation and its accompanying risks, a major concern for patients and practitioners alike. (3) The concern about QT prolongation and torsade de pointes proarrhythmia is certainly valid for current class III agents, but it is not a concern with class IC drugs, which was misstated in the report. (4) The data set of the drugs considered was thought to be small; yet, it is substantially larger than the pivotal trials that resulted in Food and Drug Administration approval for flecainide, propafenone, and sotalol for treatment of AF. (5) Perhaps most importantly, the issue of watchful waiting should really be a nonissue, because that is inherently what was done in the placebo arms of the trials reviewed in the report. (6) In addition, although the authors note that direct current (DC) cardioversion could be performed and that when done after drug failure, it did allow the total number of patients attaining sinus rhythm to be essentially similar in the drug and placebo groups, the authors did not address several substantial items. These include the risks and costs associated with DC shock in this setting; the risks and costs associated with the anesthesia required for DC cardioversion; the fact that the total costs exceed those of pharmacological cardioversion; the skin discomfort that often follows DC cardioversion; and the need to reevaluate implanted devices after DC shock if such are present. DC cardioversion is not a panacea; moreover, it can happen that emergent (but not instantaneously emergent) cardioversion is sometimes needed but anesthesia for DC shock is contraindicated. In such cases, pharmacological conversion with an intravenous agent is the clinical procedure of choice, and a safer choice than ibutilide remains a clinical necessity for practitioners. Thus, I believe the overall risk-to-benefit profile as noted by the committee according to the report may have been calculated in a biased manner against the drugs that were considered, at least as far as vernakalant goes.DisclosuresDr Reiffel has served on the advisory board and/or speakers’ bureau for Astellas Pharma, Cardiome, GlaxoSmithKline, Pharmacia, Reliant Pharmaceuticals, CV Therapeutics, and Sanofi-Aventis.Reference1 Hiatt WR, Lincoff AM, Harrington RA. Acute pharmacological conversion of atrial fibrillation to sinus rhythm: is short-term symptomatic therapy worth it? A report from the December 2007 Meeting of the Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration. Circulation. 2008; 117: 2956–2957.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails January 27, 2009Vol 119, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.806273PMID: 19171861 Originally publishedJanuary 27, 2009 PDF download Advertisement

Response to Letter Regarding Article, “Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm”

We appreciate the comments by Dr Reiffel about our report1 from the Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee Meeting, December 2007, which reviewed 2 development programs for the acute pharmacological conversion of atrial fibrillation. On the basis of his letter, we would like to clarify several points. The deliberations and recommendations of FDA advisory panels are focused on the development program under review and therefore do not serve as …

Acute Pharmacological Conversion of Atrial Fibrillation to Sinus Rhythm

Atrial fibrillation is a common arrhythmia that affects >2 million adults in the United States, with ≈160 000 new cases diagnosed each year. Although many patients are asymptomatic, those with symptoms can experience palpitations, dyspnea, angina, exertional fatigue, and presyncope. The long-term consequences of atrial fibrillation are well described and include increased risk of thromboembolic events that require chronic anticoagulation in most patients. Reestablishment of sinus rhythm is a key long-term management strategy that would be expected to relieve symptoms, improve hemodynamics, and reduce the risk of thromboembolic complications. Cardioversion is recommended for patients with relatively new-onset atrial fibrillation who are hemodynamically unstable, have uncontrolled rapid ventricular response, or have cardiac ischemia or for acute management of symptoms.1 Options include synchronized direct current cardioversion, which requires conscious sedation to manage the discomfort of the procedure and is associated with ventricular fibrillation in 0.2% of cases, sinus bradycardia or sinus arrest in 1% of cases, and thromboembolism in 1% of cases not adequately anticoagulated.2,3 Pharmacological cardioversion is less effective than direct current cardioversion, but several drugs (dofetilide, flecainide, ibutilide, dofetilide, and propafenone) are currently approved for this indication. These drugs carry risks similar to those of electric cardioversion with the additional concerns of prolonging the QT interval and developing torsade de pointes arrhythmias. Rates of spontaneous conversion, without the attendant risks of pharmacological or electric conversion, have been reported to be as high as 73% within the first 24 hours after onset, with <50% of patients spontaneously converting after 72 hours of atrial fibrillation.4 Given this background, 2 new pharmacological agents to convert atrial fibrillation to sinus rhythm in the acute care setting were reviewed by the Cardiovascular and Renal Drugs Advisory Committee of …

Transvenous electrical cardioversion of atrial fibrillation in six horses using custom made cardioversion catheters

Pharmacological conversion of atrial fibrillation (AF) to sinus rhythm in horses can be difficult. The objective of this study was to investigate the feasibility of transvenous electrical cardioversion with custom made catheters in eight horses, of which three had failed cardioversion using quinidine sulfate. Two cardioversion catheters and one pacing/sensing electrode were inserted via the right jugular vein and placed using ultrasound guidance into the left pulmonary artery, the right atrium and the right ventricle, respectively. Because immediate recurrence of AF was encountered in the second horse treated, pre-treatment with amiodarone was given to each of the remaining six horses. Induction of general anaesthesia was associated with dislocation of the cardioversion catheter in three horses, requiring a second catheterisation procedure. During general anaesthesia, biphasic R wave synchronised shocks of up to 360 J were delivered between both cardioversion electrodes. In six horses (75%), including two which had failed quinidine sulfate treatment, sinus rhythm was restored with a mean energy level of 295 ± 62 J. No side effects were observed. Blood analysis 3 h after cardioversion revealed normal parameters, including cardiac troponin I values. Transvenous electrical cardioversion of atrial fibrillation with custom made cardioversion catheters can be considered as a treatment option for atrial fibrillation in horses, especially when conventional drugs fail.

Dofetilide: a new class III antiarrhythmic agent

Dofetilide is a relatively new class III antiarrhythmic agent that selectively blocks the rapid component of the cardiac ion channel delayed rectifier current. This results in an increase in the action potential duration and effective refractory period of the myocyte, thereby terminating reentrant tachyarrhythmias and preventing their re-induction. Oral dofetilide is effective in the conversion of atrial fibrillation and flutter to sinus rhythm and in the maintenance of sinus rhythm after conversion. It is generally well tolerated but like other antiarrhythmic agents in its class, torsades de pointes may be induced as a consequence of therapy. This risk is minimized by dosage adjustment according to creatinine clearance and QTc interval, by selecting patients without known risk factors for torsades and by initiating treatment in a monitored hospital setting for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure, hence its importance as an alternative medication for the pharmacological conversion of atrial fibrillation and flutter, and maintenance of sinus rhythm after conversion in patients at high risk of sudden death.

Ibutilide to expedite ED therapy for recent-onset atrial fibrillation flutter

Objective Ibutilide is a type III antiarrhythmic agent approved for the pharmacologic conversion of atrial fibrillation (AF) and atrial flutter (AFl). Previous studies conducted outside the ED setting have demonstrated conversion rates of 60% to 80%. This response has been highest in patients with recent-onset AF-AFl. These observations and the 4-hour half-life of ibutilide suggest that it may be an excellent drug with which to treat AF-AFl in the ED. The purpose of the study was to examine the efficacy and safety of ibutilide in terminating AF-AFl in patients who present to the ED with symptoms of less than 3 days' duration, neither angina nor heart failure, and no comorbid conditions that require admission. Methods Among 36 enrolled patients, the admission electrocardiogram demonstrated AF in 26 and AFl in 10. Ibutilide 1 mg was administered intravenously for 10 minutes. If sinus rhythm was not present 10 minutes after the infusion concluded, a second infusion of 1 mg was given. Successful conversion was defined as restoration of sinus rhythm within 1 hour after the last dose of ibutilide. Results Sixteen (61.5%) of 26 patients with AF and 9 (90%) of 10 patients with AFl converted to sinus rhythm (overall conversion rate = 69%). The mean time to arrhythmia termination was 19 ± 9 minutes. The mean stay in the ED was 16.2 hours. No significant complications occurred. Conclusion We conclude that ibutilide is an excellent therapy option for restoring sinus rhythm in the ED. Its use may obviate the need for admission, avoid the risks and inconveniences of general anesthesia to perform electrical cardioversion, and reduce the ED length of stay in selected patients with recent-onset atrial arrhythmias.

The Role of Late INa and Antiarrhythmic Drugs in EAD Formation and Termination in Purkinje Fibers

Multiple components of cardiac Na current play a role in determining electrical excitation in the heart. Recently, the role of nonequilibrium components in controlling cardiac action potential plateau duration, and their importance in regulating the occurrence of afterdepolarizations and arrhythmias have garnered more attention. In particular, late Na current (late I(Na)) has been shown to be important in LQT2 and LQT3 arrhythmias. Class III agents like dofetilide, clofilium, and sotalol, which can all cause a drug-induced form of LQT2, significantly lengthen action potential duration at 50% and 90% repolarization in isolated rabbit Purkinje fibers, and can initiate the formation of early afterdepolarizations, and extra beats. These actions can lead to the development of a serious ventricular tachycardia, torsades de pointes, in animal models and patients. However, pretreatment with agents that block late I(Na), like lidocaine, mexiletine, and RSD1235, a novel mixed ion channel blocker for the rapid pharmacologic conversion of atrial fibrillation, significantly attenuates the prolonging effects of Class III agents or those induced by ATX-II, a specific toxin that delays Na channel inactivation and amplifies late I(Na) greatly, mimicking LQT3. The Na channel block caused by lidocaine and RSD1235 can be through the open or inactivated states of the channel, but both equivalently inhibit a late component of Na current (I(Na)), recorded at 22 degrees C using whole-cell patch clamp of Nav 1.5 expressed in HEK cells. These protective actions of lidocaine, mexiletine, and RSD1235 may result, at least in part, from their ability to inhibit late I(Na) during action potential repolarization, and inhibition of the inward currents contributing to EAD and arrhythmia formation.

Conversion of Recent‐Onset Atrial Fibrillation or Flutter with Amiodarone after Ibutilide Has Failed: A Rapid, Efficient, and Safe Algorithm

Ibutilide and amiodarone are used for the pharmacological conversion of atrial fibrillation (AF) or flutter (AFl), but their efficacy is rather moderate. To test whether the use of ibutilide as a first-choice drug and of amiodarone as a second-line treatment provides a rapid, effective, and safe algorithm for conversion of recent-onset AF or AFl to sinus rhythm (SR), 85 consecutively recruited patients (59 women; mean age 69.7+/-0.9 years) with AF or AFl of recent onset received 1 or 2 mg of ibutilide infusion. In the case of ibutilide failure, amiodarone was given (6 mg/kg IV infusion over 60 minutes followed by 1200 mg IV infusion over 24 hours) 4 hours later. Ten patients with AF or AFl of recent onset were used as controls. The maximum rate-corrected QT interval was calculated in all patients and controls before the start of the study (baseline electrocardiogram (ECG)), 30 minutes later (30-min ECG), and 4 hours later (4-h ECG). Fifty-eight (68%) patients reversed to SR within the first 4 hours after the end of ibutilide infusion. In those 27 patients in whom ibutilide failed, amiodarone was given. Twenty-four of them (28%) were converted to SR during amiodarone infusion. Therefore, in total, 82 (96%) patients with recent-onset AF or AFl were converted to SR. The 10 controls were monitored for the same time period as the study patients and 5 (50%) out of them were spontaneously converted to SR (P<0.0001). No pro-arrhythmia or any other side effects were noticed in the study patients or in the controls. QTc was moderately decreased before the start of amiodarone infusion in patients group, while it did not differ among the three ECGs in controls. The combination of ibutilide as a first-choice drug and of amiodarone infusion in the case of ibutilide failure provides an effective, rapid, and safe algorithm for restoration of SR in patients with AF or AFl of recent onset.

Ibutilide to expedite Emergency Department therapy of recent onset atrial fibrillation - flutter

PURPOSE: Ibutilide is a type III antiarrhythmic agent for the pharmacological conversion of atrial fibrillation (AF) and flutter (AFl). Previous studies conducted outside the Emergency Department (ED) setting have demonstrated conversion rates of 60 to 80%. This response has been highest in patients with recent onset AF. These observations and Ibutilide's 6-hour half-life, suggest that it may be an excellent drug with which to treat AF-AFl in the ED. The purpose of this study was to examine Ibutilide's efficacy in terminating AF-AFl in patients who present to the ED with symptoms of < 3 days’ duration, neither angina nor heart failure and no co-morbid condition that required admission.

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (IV) procainamide, high-dose IV or high-dose combination IV and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, IV ibutilide is more effective than placebo and IV procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred IV agent and propafenone a preferred oral agent. For conversion of recent onset AF of longer duration (less than 90 days), IV ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed.