Conversion Of Persistent Atrial Fibrillation Research Articles

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 <48h vs others: 75.3% vs 12.0%, p < 0.001). In multivariable logistic regression model AF duration (for every 24h in AF - OR = 0.97; 95% CI 0.96 – 0.98), the left atrium antero-posterior diameter (OR = 0.92; 95% CI 0.86 – 0.99) and the serum creatinine level (OR = 0.15; 95% CI 0.03 – 0.73) were identified as independent predictors of antazoline based pharmacological cardioversion effectiveness, even after adjustment for comorbidities. The ROC curves revealed that the optimal cut-off value for AF duration time predicting ANT’s effectiveness was 48h (AUC = 0.876; 95% CI 0.815 – 0.922). There were only one episode of bradycardia <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 (<48 hours) and in patients without the left atrium enlargement and significant renal disease. Abstract Figure.

Pretreatment with intravenous amiodarone improves the efficacy of ibutilide treatment on cardioversion rate and maintenance time of sinus rhythm in patients with persistent atrial fibrillation.

The aim of the present study was to assess the efficacy and safety of the pharmacological conversion of persistent atrial fibrillation (AF) using amiodarone or/and ibutilide. Seventy-nine consecutive patients (48 males and 31 females; mean age, 64.6±11.2 years; range, 40-80 years) with non-valvular chronic AF lasting >7 days (range, 7-97 days) that were admitted to hospital for elective pharmacological cardioversion were randomly assigned to receive treatment with intravenous ibutilide (1 mg plus an additional 1 mg if required; n=39) or intravenous amiodarone (300 mg) plus intravenous ibutilide (1 mg; n=40). Success rates of cardioversion were 51.3% (20/39 patients) for ibutilide alone and 71.8% (28/39 patients) for amiodarone + ibutilide (P<0.05). A comparable increase in the QTc interval was observed in the two groups. It was observed that the co-administration of amiodarone and ibutilide was safer than ibutilide alone with regard to the risk of ventricular arrhythmia. Forty-eight patients of successful cardioversion were personally contacted for follow-up. The result indicated that the sinus rhythm maintenance time of the amiodarone + ibutilide group (4.36±2.44 months) was significantly higher than that of the ibutilide group (2.34±1.75 months; P<0.01). In conclusion, pretreatment with intravenous amiodarone + ibutilide for pharmacological cardioversion of persistent AF is considered to be more effective and safer than treatment with ibutilide alone.

Conversion of persistent atrial fibrillation to sinus rhythm after LAA ligation with the LARIAT device

Conversion of persistent atrial fibrillation to sinus rhythm after LAA ligation with the LARIAT device

Predictors of sinus rhythm after electrical cardioversion of atrial fibrillation: results from a data mining project on the Flec-SL trial data set.

Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset. The primary outcome was time to persistent AF or death. The RIMARC algorithm calculated the predictive weights of each variable in the Flec-SL dataset for the primary outcome. Among the initial 21 parameters, 6 variables were identified by the RIMARC algorithm. In univariate Cox regression analysis of these variables, increased heart rate during AF and successful pharmacological conversion (PC) to sinus rhythm (SR) were found to be significant predictors. Multivariate Cox regression analysis revealed successful PC as the single relevant predictor of SR maintenance. The primary outcome risk was 3.14 times (95% CI:1.7-5.81) lower in those who had successful PC to SR than those who needed electrical cardioversion. Pharmacological conversion of persistent AF with flecainide without the need for electrical cardioversion is a powerful and independent predictor of maintenance of SR. A strategy of flecainide pretreatment for 48 h prior to planned electrical cardioversion may be a useful planning of a strategy of long-term rhythm control.

Catheter Ablation for Persistent and Long-Standing Persistent Atrial Fibrillation.

Persistent and long-standing persistent atrial fibrillation evolves from complex arrhythmogenic substrate and sources. Multiple studies have shown improved freedom from arrhythmia recurrences if sinus rhythm had been restored during the index ablation; however, such harder procedural endpoint requires laborious stepwise approach almost invariably pursuing non-pulmonary-vein sources. Longer-term conversion of persistent atrial fibrillation into sinus rhythm is associated with significant improvement in major indices of hemodynamic and functional status; these indices also represent major predictors of cardiovascular mortality. Optimal ablation techniques and strategies preserving most of the individual potential for functional improvement need to be established.

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.

GW25-e5252 Inhibitory Effects of Dronedarone on Small Conductance Calcium Activated Potassium Channels in Patients with Chronic Atrial Fibrillation: Comparison to Amiodarone

Small conductance calcium activated potassium channels (SK) were found closely related to Atrial Fibrillation (AF). Dronedarone is recently used for the patients with paroxysmal AF or after conversion of persistent AF. The purpose of this study was to confirm the inhibitory effects of dronedarone on

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.

Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations)

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

Abstract 358: Impaired Function of Circulating Cd34 + Cd45 - Cells in Patients with Persistent Atrial Fibrillation Is Restored by the Calcium Channel Blocker Bepridil Hydrochloride

Background: Despite accumulating evidence regarding the occurrence of endothelial dysfunction in persistent atrial fibrillation (PAF) patients, little is still known about the number and function of circulating endothelial progenitor cells (EPCs) in PAF. Bepridil hydrochloride (BEP) is a multiple ion channel blocker that has exhibited efficacy for the pharmacological conversion of PAF. Methods and Results: We evaluated both the number and functional properties of CD34 + CD45 - cells as EPCs in 12 consecutive patients with PAF. The number of circulating EPCs was determined by flow cytometry. BEP was administered beginning at a daily dose of 100 mg and was increased up to a maximum of 200 mg for 30 days. Higher levels of circulating CD34 + CD45 - cells were observed in patients with PAF in comparison to the control subjects [ 0.35 +0.04% vs 0.14 + 0.03% CD34 + CD45 - cells in the MNC fraction, p&lt;0.048]. However, the EPCs from patients with PAF exhibited an impaired migration towards SDF-1. Conclusion: The number of EPCs was observed to increase, but the EPC function was impaired in patients with persistent AF. BEP may have a beneficial effect on the pharmacological conversion of PAF by helping to restore the EPC function.

Conversion of Persistent Atrial Fibrillation After Radiofrequency Ablation by Ibutilide.

Ablation of peristent AF remains challenging with questions unanswered about what the ideal next step after pulmonary venous isolation should be. Ibutilide is a highly effective class III agent for cardioversion of acute-onset atrial flutter and fibrillation, with limited clinical use due to risks of ventricular pro-arrhythmias. However, results from the on-going MAGIC-AF trial may re-invigorate its role in clinical electrophysiology as an invaluable adjunct to facilitate controlled substrate modification during ablation of persistent AF.

ORAL PRESENTATION

ORAL PRESENTATION

The Efficacy and Characteristics of Intraprocedural Use of Ibutilide during Stepwise Linear Catheter Ablation of Persistent Atrial Fibrillation

Objective: Ibutilide is commonly used for acute conversion of atrial fibrillation (AF) and flutter. The purpose of this study was to determine the efficacy and safety of ibutilide for the rapid conversion of persistent AF during the procedure of radiofrequency catheter ablation (RFCA).Methods: Ibutilide was administered intravenously to 58 consecutive persistent AF patients which failed to restore sinus rhythm (SR) after extensive linear RFCA. The mean duration of AF was 15.5±18.9 months. Blood pressure and corrected QT (QTc) interval were continuous monitored.Results: There were 46 (79.3%) patients converted to sinus rhythm (SR) by infusion of Ibutilide after RFCA with mean conversion times of 12.5±9.9 min. The mean dosage was 1.06±0.33 mg. 28 (48.3%) patients experienced left atrial flutter (LAFL) before restoration of SR. There was a statistically significant prolongation in QTc interval after 5 minutes of infusion (from 452.5 ms to 506.4 ms, P<0.001). No patient experienced sustained ventricular arrhythmias or torsades de pointe. During a median follow up of 32 months, 62.1% of patients were free from AF or LAFL.Conclusion: Ibutilide is safe and effective in sinus rhythm restoration in the procedure of persistent atrial fibrillation catheter ablation.

Rapid Conversion of Persistent Atrial Fibrillation to Sinus Rhythm by Intravenous AZD7009

This randomized, double-blind trial compared cardioversion rates between AZD7009 infusion (15-minute 3.25 mg/min, 15-minute 4.4 mg/min, or 30-minute 3.25 mg/min) and placebo infusion (15 or 30 minutes) in patients with atrial fibrillation (AF) scheduled for DC cardioversion. One hundred sixty-eight patients were randomized, 167 received study treatment, and 159 were included in perprotocol analyses. The mean duration of current AF episode was 47 days (range, 0.8-92). In the AZD7009 30-minute 3.25 mg/min group, 21 of 42 patients converted within 90 minutes, compared with 7 of 39, 7 of 36, and 0 of 42 patients in the 15-minute 3.25 mg/min, 15-minute 4.4 mg/min, and combined placebo groups, respectively. Patients not converted within 90 minutes underwent DC cardioversion. In patients with AF episodes </=30 days, conversion rates with AZD7009 30-minute 3.25 mg/min and after placebo followed by DC cardioversion were 82% and 83%, respectively. AZD7009 was generally well tolerated. Mean QTc increased by 15% to 20% in the AZD7009 treatment groups. One patient experienced a ventricular tachyarrhythmia of 7 beats, with features of torsades de pointes. AZD7009 was associated with a 50% conversion rate in the best-dose group. In patients with AF episodes <or=30 days, the conversion rates after AZD1305 and placebo followed by DC cardioversion were observed to be similar.

Effect of cardiac resynchronization therapy on conversion of persistent atrial fibrillation to sinus rhythm

Spontaneous conversion of persistent atrial fibrillation to sinus rhythm (SR) has anecdotally been reported following cardiac resynchronisation therapy. This monocenter observational study was designed to estimate the incidence of spontaneous conversion of persistent atrial fibrillation to SR in consecutive patients implanted with a cardiac resynchronisation device. A total of 46 patients with persistent atrial fibrillation (> or =4 weeks pre-implant), left bundle branch block (QRS > 130 ms), left ventricular ejection fraction <0.35 and NYHA III or IV heart failure were implanted with a cardiac resynchronisation pacemaker or defibrillator and followed for at least 6 months between 6/2000 to 12/2006. During 22 +/- 9 (7-34) months of follow-up, eight out of 46 patients (17%) converted to SR. Spontaneous conversion was encountered in seven cases, whereas one patient converted due to an ICD shock delivered for ventricular tachycardia; in the latter patient, previous ICD shocks had not converted atrial fibrillation. The time interval from device implantation to conversion was 12 +/- 11 (3-31) months. In patients converting to SR, the duration of atrial fibrillation before device implantation was significantly shorter than in patients remaining in atrial fibrillation (15 +/- 13 vs. 53 +/- 58 months, P = 0.001). Echocardiographic parameters such as left ventricular ejection fraction, left ventricular end-diastolic diameter, left atrial diameter did not differ significantly between converting and non-converting patients. However, patients converting to SR showed a significant reduction in systolic pulmonary artery pressure on CRT vs. before CRT (45 +/- 13 vs. 29 +/- 5 mmHg, P = 0.008). This pilot study suggests that CRT favors spontaneous conversion of persistent AF to SR in a minority of patients. If confirmed by larger clinical studies, atrial lead implantation would be encouraged in these patients, in order to provide AV synchronous pacing in case of spontaneous conversion or successful cardioversion to SR on cardiac resynchronisation therapy.

Acute Conversion of Persistent Atrial Fibrillation During Dofetilide Initiation

Dofetilide (D) is a highly selective blocker of the rapid component of the delayed rectifier potassium current and was approved for the treatment of atrial fibrillation (AF) based on a satisfactory safety/efficacy profile from trials in patients with left ventricle (LV) dysfunction or heart failure. The dose-dependant acute conversion rates (<72 hours) were reported to be in the range of 6-30%. We hypothesized that the acute pharmacological conversion rate of D is higher than previously reported if used in a healthier cohort of patients with persistent AF. Eighty consecutive patients received D dosing per Cockroft-Gault adjustment for creatinine clearance and QTc intervals. Patients were 61 +/- 10 years, 79% male, ejection fraction (EF) 53 +/- 13%, coronary artery disease 20%, and left atrial dimension 4.1 +/- 0.2 cms. The duration of the treated AF episode was a median of 19 days (range 10-113 days). All patients received D while on telemetry for at least six dosing intervals. After 2.2 +/- 1.2 doses, 77% of patients converted to sinus rhythm (SR) and 23% did not and required direct current (DC) cardioversion. Acute pharmacological conversion rates were: 20% for D 125 mcg bid, 44% for 250 mcg bid, and 85% for 500 mcg bid. None of the patients had torsade de pointes and none had to stop D for intolerance. Failure to convert to SR on D alone was associated with larger left atrium (LA) diameter (P = 0.04), longer duration of AF (P = 0.02), and use of lower dosages of D (P = 0.04). D had an unusually high pharmacological conversion rate, demonstrated an incremental dose response, and was well tolerated and safe, in a relatively healthy adult cohort with persistent AF. In addition to D dose, pharmaco-conversion was predicted by LA size and AF duration. D is a desirable alternative for conversion of AF in a variety of clinical settings.

Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009

Acute drug conversion of persistent atrial fibrillation usually fails. The purpose of this study was to test the proarrhythmic potential, safety, and efficacy of the novel antiarrhythmic agent AZD7009 in patients with persistent atrial fibrillation (AF) or atrial flutter (mean duration 43 days) scheduled for direct current (DC) cardioversion. Patients were randomized to AZD7009 (3-hour intravenous infusion; n = 86) or placebo (n = 36). AZD7009 was given in doses intended to produce target pseudo-steady-state plasma levels of 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, or 2.5 micromol/L after 30 minutes of infusion. DC cardioversion was performed if conversion to sinus rhythm (SR) did not occur within 2 hours of infusion. AZD7009 in a concentration-dependent manner increased the rate of conversion of AF to SR and shortened the time to conversion. At the three highest target concentrations of AZD7009, 45%, 64%, and 70% of AF patients converted after a mean time of 62, 55, and 26 minutes, respectively, whereas no placebo-treated patients converted. SR was maintained for 24 hours in 21 of 22 patients with drug-associated conversion. AZD7009 treatment was associated with QT-interval prolongation; the increase in QT corrected according to Fridericia typically ranged from 40 to 80 ms at targeted pseudo-steady-state plasma concentrations >or=0.75 micromol/L, but a number of outliers with QT corrected according to Fridericia >550 ms were seen in the higher concentration groups, particularly after conversion to SR and prolonged infusion. None of the patients exhibited torsades de pointes according to predefined criteria; however, one patient exhibited a nonsustained, polymorphic ventricular tachycardia of eight beats with torsades de pointes-like features after AZD7009 infusion (asymptomatic and discovered only upon retrospective Holter tape analysis). Clinical adverse events (primarily dizziness, bradycardia, hypotension, and nausea) were significantly more common in the highest target concentration AZD7009 group vs placebo (P <.001). AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.

Importance of left atrial diameter and atrial fibrillatory frequency for conversion of persistent atrial fibrillation with oral flecainide

This study sought to evaluate the efficacy and tolerability of oral flecainide beginning with a 300-mg bolus in patients with atrial fibrillation (AF) lasting >24 hours. The focus of this study, however, was to relate patient characteristics including echocardiographic parameters and fibrillatory frequency obtained from the surface electrocardiogram to conversion rate. Fibrillatory frequency was chosen as a marker of electrical remodeling, because it represents atrial refractoriness,1 thereby reflecting AF complexity.2 Furthermore, fibrillatory frequency obtained from intra-atrial recordings3 or the surface electrocardiogram4 has been shown to predict AF conversion success using intravenous ibutilide.

Effects of diltiazem pretreatment on direct-current cardioversion in patients with persistent atrial fibrillation: A single-blind, randomized, controlled study

Background Electric conversion of atrial fibrillation is the most widely used and effective treatment for sinus rhythm restoration. However, it has a limited success rate and a high recurrence rate. Hypothesis Pretreatment with calcium channel blocker may improve the efficacy by reversing the so-called “electric remodeling” phenomenon, also related to overload in cytosolic calcium. Methods The efficacy of diltiazem or amiodarone pretreatment (oral, 1 month before and 1 month after conversion) on direct-current conversion of persistent atrial fibrillation was assessed in 120 patients, randomly assigned to 3 matched groups: A (n = 44, diltiazem); B (n = 46, amiodarone), and C (n = 30, digoxin). Results Before electric conversion, all treatments significantly decreased mean heart rate. Spontaneous conversion to sinus rhythm was achieved in 6% of patients of group A (3 of 46) versus 25% of group B (11 of 44) and 3% (1 of 30) of group C (A/C vs B, P <.005). Current conversion was more successful in group B (91%) compared with group A (76%) and group C (67%) (B vs A/C, P <.05), with no difference in the electric threshold for effective conversion (P = not significant). At the 24-hour time point, early relapse of atrial fibrillation was similar between groups A and B (A, 2%; B, 3%; P = not significant) and lower than group C (12%) (P <.01), whereas at the 1-month time point the recurrence rate was lower in group B (28%) versus groups A (56%) and C (78%) (B vs A/C, P <.01). No significant side effects were reported. Conclusions Although diltiazem seems to be as effective as amiodarone in reducing early atrial fibrillation recurrences, diltiazem is less effective in determining spontaneous or electric conversion, with a higher recurrence rate at 2 months. Diltiazem pretreatment could be considered as only a second choice treatment in those patients in whom amiodarone is contraindicated. (Am Heart J 2000;140:e12.)

Efficacy of amiodarone for the termination of persistent atrial fibrillation

The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64 ± 9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9 ± 7.2 vs 50.4 ± 5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.