title: Amiodarone versus propafenone for conversion of chronic atrial fibrillation: results of a randomized, controlled study. A Randomized Comparison of External and Internal Cardioversion of Chronic Atrial Fibrillation Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. Clonidine for patients with rapid atrial fibrillation. Efficacy and safety of intravenous diltiazem for treatment of atrial fibrillation and atrial flutter. The Diltiazem-Atrial Fibrillation/Flutter Study Group. Efficacy and safety of intravenous dofetilide for rapid termination of atrial fibrillation and atrial flutter. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. Effects of atenolol, verapamil, and xamoterol on heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation. Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study. Effect of orally administered celiprolol in patients with chronic atrial fibrillation. Clinical course of recent-onset atrial fibrillation treated with oral propafenone. Primary prevention of arterial thromboembolism in non-rheumatic atrial fibrillation in primary care: randomised controlled trial comparing two intensities of coumarin with aspirin A comparison of treatment of atrial fibrillation with low-energy intracardiac cardioversion and conventional external cardioversion. A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. Intravenous propafenone: Efficacy and safety in the conversion to sinus rhythm of recent onset atrial fibrillation—A single-blind placebo-controlled study Efficacy and Safety of Oral Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic Atrial Fibrillation or Atrial Flutter: The Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) Study Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the veterans affairs congestive heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of Veterans Affairs CHF-STAT Investigators. Clinical value of left atrial appendage flow for prediction of long-term sinus rhythm maintenance in patients with nonvalvular atrial fibrillation. Efficacy of flecainide in patients with supraventricular arrhythmias and respiratory insufficiency Prospective comparison of flecainide versus quinidine for the treatment of paroxysmal atrial fibrillation/flutter. The Flecainide Multicenter Atrial Fibrillation Study Group. Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation. Optimal intensity of warfarin therapy for secondary prevention of stroke in patients with nonvalvular atrial fibrillation : a multicenter, prospective, randomized trial. Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention Cooperative Study Group. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. Intravenous diltiazem for the treatment of patients with atrial fibrillation or flutter and moderate to severe congestive heart failure. Efficacy of Amiodarone for the Termination of Chronic Atrial Fibrillation and Maintenance of Normal Sinus Rhythm: A Prospective, Multicenter, Randomized, Controlled, Double Blind Trial Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. Differential effects of xamoterol and verapamil on ventricular rate regulation in patients with chronic atrial fibrillation. Stroke Prevention in Atrial Fibrillation Study: Final Results Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter. A multicentre study from Stockholm. Antiarrhythmic effects of intravenous timolol in supraventricular arrhythmias Clinical use of oral verapamil in chronic and paroxysmal atrial fibrillation. Sotalol versus quinidine in the maintenance of sinus rhythm after direct current conversion of atrial fibrillation Towards improved control of atrial fibrillation. Intravenous flecainide versus verapamil for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Indobufen versus warfarin in the secondary prevention of major vascular events in nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale) Investigators. Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation. A controlled clinical study. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Maintenance of sinus rhythm after DC reversion of atrial fibrilllation. A double-blind controlled trial of long-acting quinidine bisulphate. Mechanical dysfunction of the left atrium and the left atrial appendage following cardioversion of atrial fibrillation and its relation to total electrical energy used for cardioversion. Efficacy of Dofetilide in the Treatment of Atrial Fibrillation-Flutter in Patients With Reduced Left Ventricular Function: A Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) Substudy Randomised double blind trial of oral versus intravenous flecainide for the cardioversion of acute atrial fibrillation Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled study. Transthoracic cardioversion of atrial fibrillation: comparison of rectilinear biphasic versus damped sine wave monophasic shocks. Amiodarone, sotalol, or propafenone in atrial fibrillation: which is preferred to maintain normal sinus rhythm? Effectiveness and safety of oral verapamil to control exercise-induced tachycardia in patients with atrial fibrillation receiving digitalis. A randomized, placebo-controlled trial of propafenone in the prophylaxis of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation. UK Propafenone PSVT Study Group. Fixed minidose warfarin and aspirin alone and in combination vs adjusted-dose warfarin for stroke prevention in atrial fibrillation: Second Copenhagen Atrial Fibrillation, Aspirin, and Anticoagulation Study. Relationships between heart rate, exercise tolerance and cardiac output in atrial fibrillation: the effects of treatment with digoxin, verapamil and diltiazem. Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study. Effect of magnesium sulfate on ventricular rate control in atrial fibrillation. Oxygen uptake kinetics and cardiopulmonary performance in lone atrial fibrillation and the effects of sotalol. Acute pharmacologic conversion of atrial fibrillation and flutter: the role of flecainide, propafenone, and verapamil. Intravenous administration of diltiazem in the treatment of supraventricular tachyarrhythmias. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study. Digoxin for converting recent-onset atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Low-dose amiodarone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Biphasic versus monophasic shock waveform for conversion of atrial fibrillation: the results of an international randomized, double-blind multicenter trial. Verapamil improves exercise capacity in chronic atrial fibrillation: double-blind crossover study. Maintenance of sinus rhythm with oral d,l-sotalol therapy in patients with symptomatic atrial fibrillation and/or atrial flutter. d,l-Sotalol Atrial Fibrillation/Flutter Study Group. Emergency management of atrial fibrillation and flutter: intravenous diltiazem versus intravenous digoxin. Long-term follow-up of direct current cardioversion after cardiac surgery with special reference to quinidine1 Comparative effects of nadolol-digoxin combination therapy and digoxin monotherapy for chronic atrial fibrillation. Beta-adrenoceptor blockers in atrial fibrillation: the importance of partial agonist activity. Perceived exertion and gas exchange after calcium and beta-blockade in atrial fibrillation. Intravenous sotalol for the termination of supraventricular tachycardia and atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled study. Sotalol Multicenter Study Group. A controlled study on oral propafenone versus digoxin plus quinidine in converting recent onset atrial fibrillation to sinus rhythm. Conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm: the effect of no treatment and high-dose amiodarone. A randomized, placebo-controlled study. Efficacy and safety of sotalol versus quinidine for the maintenance of sinus rhythm after conversion of atrial fibrillation. SOCESP Investigators. The Cardiology Society of São Paulo. Prophylaxis of embolic events in patients with atrial fibrillation using low molecular weight heparin. Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial. Intravenous amiodarone versus verapamil for acute conversion of paroxysmal atrial fibrillation to sinus rhythm. A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Efficacy of intravenous ibutilide for rapid termination of atrial fibrillation and atrial flutter: a dose-response study. Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone. Intravenous propafenone for converting recent onset atrial fibrillation in emergency departments: a randomized placebo-controlled multicenter trial. FAPS Investigators Study Group. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. Intravenous propafenone in paroxysmal atrial fibrillation: A randomized, placebo‐controlled, double‐blind, multicenter clinical trial Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study. Prevalence of atrial fibrillation in elderly subjects (the Cardiovascular Health Study). Efficacy of intravenous magnesium sulphate in supraventricular tachyarrhythmias. Propafenone for conversion of recent-onset atrial fibrillation. A controlled comparison between oral loading dose and intravenous administration. Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo. Propafenone versus amiodarone in field treatment of primary atrial tachydysrhythmias. Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation RISK OF STROKE IN NON-RHEUMATIC ATRIAL FIBRILLATION Comparison of sotalol with digoxin-quinidine for conversion of acute atrial fibrillation to sinus rhythm (the Sotalol-Digoxin-Quinidine Trial). Digoxin infusion versus bolus injection in rapid atrial fibrillation: relation between serum level and response Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial Atrial fibrillation and flutter. Immediate control and conversion with intravenously administered verapamil. Effectiveness of amiodarone as a single oral dose for recent-onset atrial fibrillation. Oral Propafenone To Convert Recent-Onset Atrial Fibrillation in Patients with and without Underlying Heart Disease Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. PAFIT-3 Investigators. The Propafenone in Atrial Fibrillation Italian Trial. Comparisons of oral propafenone and sotalol as an initial treatment in patients with symptomatic paroxysmal atrial fibrillation. Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: A randomized, double-blind study Prospective comparison of flecainide versus sotalol for immediate cardioversion of atrial fibrillation. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Conversion efficacy and safety of repeated doses of ibutilide in patients with atrial flutter and atrial fibrillation. Study Investigators. Magnesium therapy in new-onset atrial fibrillation. Placebo controlled trial of xamoterol versus digoxin in chronic atrial fibrillation. Digoxin or verapamil or metoprolol for heart rate control in patients with mitral stenosis--a randomised cross-over study. Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group. Evaluation of outpatient initiation of antiarrhythmic drug therapy in patients reverting to sinus rhythm after an episode of atrial fibrillation. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Effects of nadolol on the spontaneous and exercise-provoked heart rate of patients with chronic atrial fibrillation receiving stable dosages of digoxin. Modulation of ventricular rate in permanent atrial fibrillation: Randomized, crossover study of the effects of slow‐release formulations of gallopamil, diltiazem, or verapamil Conversion of atrial flutter by ibutilide is associated with increased atrial cycle length variability. Ventricular rate control and exercise performance in chronic atrial fibrillation: effects of diltiazem and verapamil. Usefulness of labetalol in chronic atrial fibrillation. The effect of magnesium versus verapamil on supraventricular arrhythmias Intravenous flecainide versus amiodarone for recent-onset atrial fibrillation. Comparison of intravenous flecainide, propafenone, and amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Conversion of recent onset atrial fibrillation to sinus rhythm using a single oral loading dose of propafenone: comparison of two regimens. Comparative efficiency of quinidine and verapamil in the maintenance of sinus rhythm after DC conversion of atrial fibrillation. A controlled clinical trial. Comparison of the safety and efficacy of flecainide versus propafenone in hospital out-patients with symptomatic paroxysmal atrial fibrillation/flutter. The Flecainide AF French Study Group. Effectiveness of intravenous propafenone for conversion of recent‐onset atrial fibrillation: A placebo‐controlled study The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter. A Comparison of Amiodarone and Digoxin in the Treatment of Atrial Fibrillation Complicating Suspected Acute Myocardial Infarction Effects of diltiazem, propranolol, and their combination in the control of atrial fibrillation A comparison of rate control and rhythm control in patients with atrial fibrillation. Intravenous propafenone versus intravenous amiodarone in the management of atrial fibrillation of recent onset: a placebo-controlled study. A comparison of digoxin, diltiazem and their combination in the treatment of atrial fibrillation. Effectiveness of loading oral flecainide for converting recent-onset atrial fibrillation to sinus rhythm in patients without organic heart disease or with only systemic hypertension. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study Xamoterol improves the control of chronic atrial fibrillation in elderly patients. Embolic events in patients with atrial fibrillation and effective anticoagulation: value of transesophageal echocardiography to guide direct-current cardioversion. Final results of the Ludwigshafen Observational Cardioversion Study. Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA study. The College of French Cardiologists. Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. The impact of patients' preferences on the treatment of atrial fibrillation: observational study of patient based decision analysis. Relative efficacy of oral verapamil and digoxin alone and in combination for the treatment of patients with chronic atrial fibrillation. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial Comparison of flecainide and procainamide in cardioversion of atrial fibrillation. Effectiveness of fixed minidose warfarin in the prevention of thromboembolism and vascular death in nonrheumatic atrial fibrillation. Intravenous digoxin in acute atrial fibrillation. Results of a randomized, placebo-controlled multicentre trial in 239 patients. The Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Diagnostic accuracy of transesophageal echocardiography for detecting left atrial thrombi in patients with rheumatic heart disease having undergone mitral valve operations. Superiority of ibutilide (a new class III agent) overdl-sotalol in converting atrial flutter and atrial fibrillation Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. The efficacy of anticoagulant therapy in preventing embolism related to D.C. electrical conversion of atrial fibrillation. Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators. Effects of amiodarone versus quinidine and verapamil in patients with chronic atrial fibrillation: results of a comparative study and a 2-year follow-up. Accuracy of biplane transesophageal echocardiography in detecting left atrial thrombus. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Improved control of atrial fibrillation with combined pindolol and digoxin therapy. Double-blind evaluation of practolol and quinidine in the treatment of chronic atrial fibrillation. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.
abstract: OBJECTIVES The purpose of this study was to investigate the efficacy and safety of amiodarone and propafenone in the conversion of  chronic atrial fibrillation  in a prospect i ve , r and omized , placebo-controlled study . BACKGROUND The effectiveness of amiodarone and propafenone in the treatment of patients with chronic atrial fibrillation has not been adequately studied . METHODS One hundred one patients ( 48 men , mean age 64 + /- 9 years ) with atrial fibrillation lasting > 3 weeks participated in the study . Thirty-four patients received amiodarone ( 300 mg intravenously over 1 h , followed by 20 mg/kg over the next 24 h plus 600 mg orally , in three doses , for 1 week , then 400 mg/day orally , for three weeks ) , 32 received propafenone ( 2 mg/kg intravenously over 15 min , followed by 10 mg/kg over 24 h and then 450 mg/day orally , for one month ) and the remaining 35 served as control subjects . All patients received digoxin and anticoagulant treatment as indicated ( International Normalized Ratio 2 to 3 ) . RESULTS Conversion to sinus rhythm was achieved in 16 ( 47.05 % ) patients who received amiodarone , in 13 ( 40.62 % ) who received propafenone and in none of the control subjects ( p < 0.001 for both groups vs. control subjects ) . Those who converted had smaller atria than those who did not and atrial fibrillation of shorter duration in both the amiodarone and propafenone groups . Treatment was discontinued in one patient of the propafenone group because of significant QRS widening . CONCLUSIONS Amiodarone and propafenone appear to be safe and equally effective in the termination of chronic atrial fibrillation . Left atrial diameter and arrhythmia duration are independent predictors of conversion Background Delivery of shocks within the right atrium has been reported to be more effective than conventional external shocks in converting atrial fibrillation ( AF ) , but these two cardioversion techniques have never been compared prospect ively . The purpose of this study was to compare the efficacies of external and internal cardioversion in patients with chronic AF unresponsive to prior attempts at electrical and /or pharmacological cardioversion . Low-dose amiodarone was used in all patients after cardioversion to suppress recurrences of AF . Methods and Results One hundred twelve patients with AF of at least 1 month in duration were r and omly assigned to undergo external cardioversion with 300–360-J shocks or internal cardioversion with 200–300-J shocks delivered through a st and ard electrode catheter within the right atrium . The patients were treated with amiodarone ( 200 mg/day 5–7 days/week ) for 1 month before electrical cardioversion and afterward if the cardioversion was successful . The patients were-evaluated at regular intervals during 1 year of follow-up . The efficacy of internal cardioversion was significantly greater than that of external cardioversion ( 91 % versus 67 % , p = 0.002 ) . The only variable that was associated with the outcome of cardioversion was body weight . Among patients in whom sinus rhythm was restored , AF recurred as often after internal and external cardioversion ; at 1 year of follow-up , 37 % of patients in whom external or internal cardioversion had been effective were still in sinus rhythm .  Patients who had undergone an attempt at electrical cardioversion before entry into this study were less likely to remain in sinus rhythm after cardioversion . The only complications of cardioversion were one instance of cerebral thromboembolism after external cardioversion and one instance of transient pulmonary edema after internal cardioversion . Therapy with amiodarone was discontinued because of an adverse drug effect in only three patients . Conclusions Internal cardioversion is more effective than external cardioversion in restoring sinus rhythm and is as safe as external cardioversion in patients with chronic AF . The recurrence rate of AF is the same after both types of cardioversion . If conventional electrical cardioversion is ineffective , internal cardioversion should be attempted . The combination of low-dose amiodarone and external or internal cardioversion may result in maintaining sinus rhythm long-term in patients with refractory AF BACKGROUND Atrial fibrillation can not always be converted to sinus rhythm by transthoracic electrical cardioversion . We examined the effect of ibutilide , a class III antiarrhythmic agent , on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion . METHODS One hundred patients who had had atrial fibrillation for a mean ( + /-SD ) of 117+/-201 days were r and omly assigned to undergo transthoracic cardioversion with or without pretreatment with 1 mg of ibutilide . We design ed a step-up protocol in which shocks at 50 , 100 , 200 , 300 , and 360 J were used for transthoracic cardioversion . If transthoracic cardioversion was unsuccessful in a patient who had not received ibutilide pretreatment , ibutilide was administered and transthoracic cardioversion attempted again . RESULTS Conversion to sinus rhythm occurred in 36 of 50 patients who had not received ibutilide ( 72 percent ) and in all 50 patients who had received ibutilide ( 100 percent , P<0.001 ) . In all 14 patients in whom transthoracic cardioversion alone failed , sinus rhythm was restored when cardioversion was attempted again after the administration of ibutilide . Pretreatment with ibutilide was associated with a reduction in the mean energy required for defibrillation ( 166+/-80 J , as compared with 228+/-93 J without pretreatment ; P<0.001 ) . Sustained polymorphic ventricular tachycardia occurred in 2 of the 64 patients who received ibutilide ( 3 percent ) , both of whom had an ejection fraction of 0.20 or less . The rates of freedom from atrial fibrillation after six months of follow-up were similar in the two r and omized groups . CONCLUSIONS The efficacy of transthoracic cardioversion for converting atrial fibrillation to sinus rhythm was enhanced by pretreatment with ibutilide . However , use of this drug should be avoided in patients with very low ejection fractions OBJECTIVE To determine whether clonidine can slow ventricular rate in patients with rapid atrial fibrillation . DESIGN R and omized , controlled trial , with a 4-hour follow-up period . SETTING Emergency room of a university hospital . PATIENTS A consecutive sample of 18 hemodynamically stable patients who were evaluated or treated for rapid atrial fibrillation . Exclusion criteria included acute or terminal illness ; current use of antiarrhythmic agents , calcium-channel blockers , or beta-blockers ; excessive hypertension ; pulmonary , valvular , or pericardial disease ; and electrolyte imbalance . INTERVENTIONS Patients were r and omly assigned to receive either " no treatment " ( control group ) or clonidine , 0.075 mg orally , at baseline and after 2 hours if heart rate did not decrease by at least 20 % . MEASUREMENTS Blood pressure was measured by the same nurse in the same arm for 4 consecutive hours , and a full 12-lead electrocardiographic evaluation was done . MAIN RESULTS Heart rate decreased to below 100 beats/min in eight of nine patients receiving clonidine compared with two of nine patients in the control group . The difference in the mean decreases in heart rate was 38 beats/min ( 95 % CI , 20 to 56 beats/min ) . Six patients who were treated with clonidine and one patient in the control group reverted to normal sinus rhythm . Systolic blood pressure decreased slightly in both groups , without significant differences . Clinical follow-up was uneventful . CONCLUSION Low-dose clonidine was an easy , efficient , and effective treatment for patients with rapid atrial fibrillation who were hemodynamically stable This study evaluates the effectiveness and safety of intravenous diltiazem for the treatment of atrial fibrillation and atrial flutter . A double-blind , parallel , r and omized , placebo-controlled protocol was used , and 6 large , urban hospitals , both university-affiliated and private , participated . The study involved 113 patients with atrial fibrillation or flutter , a ventricular rate greater than or equal to 120 beats/min and systolic blood pressure greater than or equal to 90 mm Hg without severe heart failure . The dose of intravenous diltiazem ( or identical placebo ) was 0.25 mg/kg/2 minutes followed 15 minutes later by 0.35 mg/kg/2 minutes if the first dose was tolerated but ineffective . If a patient did not respond , the code was broken and the patient was allowed to receive open-label diltiazem if placebo had been given . Of 56 patients , 42 ( 75 % ) r and omized to receive diltiazem responded to 0.25 mg/kg and 10 of 14 responded to 0.35 mg/kg , for a total response rate of 52 of 56 patients ( 93 % ) , whereas 7 of 57 patients ( 12 % ) responded to placebo ( p less than 0.001 ) . After the double-blind protocol , 49 of the 57 patients who received placebo were then given diltiazem ; 47 of 49 responded , for an overall response rate of 99 of 105 patients ( 94 % ) with diltiazem . The median time from the start of drug infusion to the maximal decrease in heart rate was 4.3 minutes . Side effects occurred in 14 patients , 7 of whom had asymptomatic hypotension not requiring intervention . Thus , intravenous diltiazem was rapidly effective for slowing the ventricular response in most patients with atrial fibrillation or atrial flutter . Blood pressure decreased slightly . Side effects were mild Dofetilide may be advantageous in terminating  atrial fibrillation/atrial flutter ( AFl )  when there are contraindications for class I drugs ( left ventricular dysfunction and /or manifest myocardial ischemia ) and beta blockers . In particular , its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF The aim of the study was to compare the effects of atenolol ( 50 mg b.i.d . ) , verapamil ( 80 mg b.i.d . ) , xamoterol ( 200 mg b.i.d . ) , and matching placebo on heart rate ( HR ) and exercise tolerance in digitalised patients with chronic atrial fibrillation . Each treatment was taken for 4 weeks , and digoxin was continued throughout the study . During treatment with placebo ( digoxin alone ) , the mean postexercise heart rate was 164 beats/min , and four subjects had rates of greater than or equal to 170 beats/min . Atenolol , verapamil , and xamoterol achieved significantly better control of exercise-induced tachycardia , mean postexercise heart rates being reduced to 120 , 131 , and 130 beats/min , respectively ( p less than 0.01 for each ) . However , minimum HRs less than or equal to 45 beats/min occurred during treatment with placebo , atenolol , and verapamil , whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min . Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance ( mean 356 m ) as compared both with placebo ( mean 421 m , p less than 0.01 ) and verapamil ( mean 439 m , p less than 0.01 ) . Xamoterol reduced maximum walking distances as compared with verapamil ( 402 vs. 439 m ; p less than 0.05 ) but not placebo ( 402 vs. 421 m ; NSS ) . Thus , atenolol , verapamil , and xamoterol achieved better control of exercise-induced tachycardia than digoxin , but atenolol clearly impaired exercise tolerance whereas verapamil did not . Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments . However , walking distances were significantly lower than those noted during treatment with verapamil BACKGROUND The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects . But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period . OBJECTIVES The purpose of this study was three-fold : ( 1 ) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on r and omized crossover study ; ( 2 ) to evaluate whether the beneficial effects of medication will be maintained after 7 months ; ( 3 ) to evaluate the safety of the combination therapy in patients with impaired left ventricular function . METHODS We did a prospect i ve r and omized crossover study in 35 patients with chronic atrial fibrillation ( AF ) including 15 patients with left ventricular dysfunction . After enrollment , each patient was evaluated for heart rate , blood pressure , rate-pressure products , maximal exercise tolerance at rest and during symptom-limited treadmill test before medication , at 4 weeks after medication of digoxin ( 0.125 - 0.5 mg daily ) with diltiazem ( 90 mg twice daily ) , and at 4 weeks after digoxin with betaxolol ( 20 mg once daily ) . We performed 24-h ambulatory electrocardiogram ( ECG ) in 15 patients at the end of each phase of treatment . We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication . RESULTS ( 1 ) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise ( 67 + /- 3 , 135 + /- 5 ( mean + /- S.E.M. ) beats/min , respectively ) in comparison to digoxin with low-dose diltiazem therapy ( 80 + /- 7 , 154 + /- 5 ) ( P < 0.05 ) . ( 2 ) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise ( 85 + /- 4 , 213 + /- 12 x 10(2 ) mmHg/min ) than in digoxin with low-dose diltiazem therapy ( 105 + /- 6 , 269 + /- 12 ) ( P < 0.05 ) . ( 3 ) Exercise capacity was significantly improved in digoxin with low-dose betaxolol ( 9.3 + /- 0.5 METS ) or digoxin with low-dose diltiazem ( 9.7 + /- 0.5 ) in comparison to control state ( 8.3 + /- 0.5 ) ( P < 0.05 ) . ( 4 ) At 7 months evaluation , there was no significant difference between at 4 weeks and at 7 months . ( 5 ) Results on 24-h ambulatory ECG showed the same findings as on treadmill test . ( 6 ) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy , they were minimal and no patient had to withdraw medication . Worsening of left ventricular dysfunction was not observed . CONCLUSION Our study suggested that ( 1 ) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products ; ( 2 ) the effects controlling ventricular rate , reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy The heart rate increase induced by dynamic exercise in patients with chronic atrial fibrillation is competitively attenuated by beta-blockade . The influence of oral celiprolol on exercise induced tachycardia was evaluated in 23 patients with chronic stable atrial fibrillation in a dose-titration study . This was succeeded by a placebo-controlled double-blind , crossover multi-center trial . During the dose-titration phase each patient underwent a single-blind three week dose escalation period-taking celiprolol 200 mg once daily for one week , celiprolol 400 mg once daily for the third week . After a one week placebo washout , patients then entered a double-blind crossover phase , consisting of one week each of placebo or celiprolol according to a pre-determined r and omization . After one week of placebo washout , each patient was crossed-over . In 21 patients celiprolol reduces exercise-induced increased heart rate by approximately 35 % when compared with placebo . These results indicate that celiprolol should be effective in controlling the exercise-induced increase in heart rate in patients with chronic atrial fibrillation . In addition , results of 24 h ambulatory ECG monitoring ( Holtor monitoring ) indicate that celiprolol reduces the ventricular premature contractions Atrial fibrillation ( AF ) is one of the most common cardiac arrhythmias in the adult population .  Propafenone is a class 1c antiarrhythmic agent that has an electrophysiologic profile suggesting that it might be potentially effective in recent-onset AF . The present study was undertaken , therefore , to examine the time course as well as the frequency of successful conversion in patients with recent-onset AF treated with propafenone administered orally . Fifty patients with recent-onset AF were recruited into 2 groups : 25 patients were given propafenone , 150 mg every 4 h , and 25 patients served as a control group and received verapamil ( a drug known to slow the ventricular response but not to restore sinus rhythm ) 40 mg , every 4 h and up to 48 h or until conversion to sinus rhythm occurred . Of the 50 patients , 2 refused to continue the study and another 2 were excluded because of left heart failure . Conversion to sinus rhythm occurred in 21 of 24 patients ( 87 percent ) in the propafenone group as compared with 9 of 22 ( 41 percent ) in the verapamil group ( p < 0.001 ) . In 10 patients in the propafenone group , conversion occurred within 12 h , within 24 h in another 9 patients , and between 24 and 48 h in the remaining 2 patients . There was no correlation between the duration of AF prior to entry into the study and the subsequent incidence of and time to conversion with propafenone . With respect to cause of AF , all groups showed a high incidence of conversion . Two patients developed heart failure during treatment and one patient ( in the verapamil group ) developed embolic stroke while still having atrial fibrillation . We conclude that in patients with AF , the prognosis for conversion to sinus rhythm within 48 h , with propafenone , is excellent ( 87 percent ) and safe Abstract Objective : To investigate the effectiveness of aspirin and coumarin in preventing thromboembolism in patients with non-rheumatic atrial fibrillation in general practice . Design : R and omised controlled trial . Participants : 729 patients aged ≥60 years with atrial fibrillation , recruited in general practice , who had no established indication for coumarin . Mean age was 75 years and mean follow up 2.7 years . Setting : Primary care in the Netherl and s. Interventions : Patients eligible for st and ard intensity coumarin ( international normalised ratio 2.5 - 3.5 ) were r and omly assigned to st and ard anticoagulation , very low intensity coumarin ( international normalised ratio 1.1 - 1.6 ) , or aspirin ( 150 mg/day ) ( stratum 1 ) . Patients ineligible for st and ard anticoagulation were r and omly assigned to low anticoagulation or aspirin ( stratum 2 ) . Main outcome measures : Stroke , systemic embolism , major haemorrhage , and vascular death . Results : 108 primary events occurred ( annual event rate 5.5 % ) , including 13 major haemorrhages ( 0.7 % a year ) . The hazard ratio was 0.91 ( 0.61 to 1.36 ) for low anticoagulation versus aspirin and 0.78 ( 0.34 to 1.81 ) for st and ard anticoagulation versus aspirin . Non-vascular death was less common in the low anticoagulation group than in the aspirin group ( 0.41 , 0.20 to 0.82 ) . There was no significant difference between the treatment groups in bleeding incidence . High systolic and low diastolic blood pressure and age were independent prognostic factors . Conclusion : In a general practice population ( without established indications for coumarin ) neither low nor st and ard intensity anticoagulation is better than aspirin in preventing primary outcome events . Aspirin may therefore be the first choice in patients with atrial fibrillation in general practice . Key messages Studies have shown that patients with non-rheumatic atrial fibrillation may benefit from anticoagulation This study in a general practice population found no benefit of st and ard or low dose anticoagulation on risk of stroke , systemic embolism , major haemorrhage , or vascular death when compared with aspirin Hypertension and age were prognostic factors for event occurrence Aspirin is the treatment of choice for preventing thromboembolism in primary care patients at low AIM Low-energy ( 1 to 15 J ) , catheter-based intracardiac cardioversion was compared with transthoracic external cardioversion ( 360 J ) in a prospect i ve , cross-over clinical trial . METHODS AND RESULTS In 187 consecutive patients with chronic atrial fibrillation , over a period of a mean of 10.0 + /- 7.3 ( SD ) months , 217 cardioversion attempts were made . Intracardiac shocks were r and omly applied between two 6-F catheters located in either the right atrium and coronary sinus or between the right atrium and left pulmonary artery . When a cardioversion attempt with one method failed , the other method was implemented . After cardioversion , all patients were treated orally with sotalol with a mean daily dose of 174 + /- 54 mg . Internal cardioversion was more effective than external cardioversion ( 65/70 = 93 % vs 92/117 = 79 % , P < 0.01 ) . The mean energy for successful cardioversion was 5.8 + /- 3.2 J for the internal and 313 + /- 71 J for the external cardioversion group . At a mean follow-up of 12.5 + /- 6.4 months , 48 % ( 38 % ) of the patients treated with internal ( external ) cardioversion were in sinus rhythm ( P < 0.05 ) . In 22 of 25 patients in whom external cardioversion failed , sinus rhythm was restored with internal cardioversion at a mean energy of 6.5 + /- 3.0 J. Overweight patients had twice the risk of unsuccessful  external cardioversion . CONCLUSIONS Internal cardioversion is effective in restoring sinus rhythm . It might be indicated in patients in whom external cardioversion had failed or in whom external cardioversion is assumed to be difficult or even contraindicated The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem .  Of the 47 patients , 44 responded to the bolus injection and were r and omized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem ( 10 to 15 mg/h ) ( 23 patients ) or placebo ( 21 patients ) for up to 24 h. Seventeen ( 74 % ) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h ( p less than 0.001 ) . Over 24 h , patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion ( p less than 0.001 ) . Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion . The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83 % ( 34 of 41 ) . Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients , those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg . However , intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter . No significant untoward effects were noted . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The effectiveness of intravenous propafenone for conversion to sinus rhythm ( SR ) of paroxysmal atrial fibrillation ( AF ) , lasting less than 7 days , was evaluated with a single-blind , r and omized , placebo-controlled study , given the possible spontaneous conversion of this arrhythmia . Group 1 ( 98 patients ) received intravenous propafenone ( 2 mg/kg iv over 10 minutes followed by 0.007 mg/kg/min ) ; and group 2 ( 84 patients )  received intravenous placebo ( 0.9 % saline solution ) . The infusion was continued until restoration of SR but no longer than 24 hours . Eight-nine patients ( 90.8 % ) received propafenone and 27 patients ( 32 % ) receiving placebo were converted to SR ( p<0.005 ) . The mean conversion time was 2.46±2.59 hours in group 1 and 17.15±5.78 hours in group 2 ( p<0.005 ) . In patients treated with propafenone , conversion of SR mostly occurred in the first 4 hours ( 86.5 % ) , considered to be the optimal infusion time in our experience . In both groups , the left atrial size was significantly larger in nonconverted than in converted patients . Similarly , the duration of the arrhythmia was significantly longer in nonconverted patients . In nonconverted patients , the mean ventricular rate decreased from 143±beats/min to 101±18 beats/min after propafenone and from 135±19 beats/min to 199 ±16 beats/min after placebo ( group 1 vs. group 2 : p<0.005 ) . Two episodes of sinus st and still ( 3.4 and 3.8 , seconds , respectively ) occurred at SR restoration obtained with propafenone . Intravenous propafenone is an effective , safe , and usually rapid drug for AF treatment . Moreover , it produces a real and significant reduction in the mean ventricular rate in nonconverted patients Background This double-blind , multicenter , placebo-controlled study determined the efficacy and safety of dofetilide in converting  atrial fibrillation ( AF ) or atrial flutter ( AFl )  to  sinus rhythm ( SR ) and maintaining SR for 1 year . Methods and Results Patients with AF or AFl ( n=325 ) were r and omized to 125 , 250 , or 500 & mgr;g dofetilide or placebo twice daily . Dosages were adjusted for QTc response and , after 105 patients were enrolled , for calculated creatinine clearance ( ClCr ) . Pharmacological cardioversion rates for 125 , 250 , and 500 & mgr;g dofetilide were 6.1 % , 9.8 % , and 29.9 % , respectively , versus 1.2 % for placebo ( 250 and 500 & mgr;g versus placebo;P = 0.015 and P < 0.001 , respectively ) . Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91 % in 36 hours . For the 250 patients who successfully cardioverted pharmacologically or electrically , the probability of remaining in SR at 1 year was 0.40 , 0.37 , 0.58 for 125 , 250 , and 500 & mgr;g dofetilide , respectively , and 0.25 for placebo ( 500 & mgr;g versus placebo , P = 0.001 ) . Two cases of torsade de pointes occurred , 1 on day 2 and the other on day 3 ( 0.8 % of all patients given active drug ) ; 1 sudden cardiac death , classified as proarrhythmic , occurred on day 8 ( 0.4 % of all patients given active drug ) . Conclusions Dofetilide , a new class III antiarrhythmic agent , is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year . In-hospital initiation and dosage adjustment based on QTc and ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk BACKGROUND In a multicenter , double-blind , placebo-controlled study , the long-term effects of amiodarone on morbidity and mortality in patients with congestive heart failure ( CHF ) and atrial fibrillation ( AF ) were evaluated during a 4-year period . METHODS AND RESULTS Of 667 patients with CHF , 103 ( 15 % ) had AF at baseline . Of these , 51 were r and omized to amiodarone and 52 to placebo . The group with sinus rhythm and the group in AF were comparable except for a higher proportion of AF in patients with nonischemic versus ischemic cardiomyopathy ( 41 % versus 27 % , P<0.005 ) . The mean ventricular response ( VR ) during AF over 24 hours was reduced by amiodarone at 2 weeks ( 20 % , P=0.001 ) , at 6 months ( 18 % , P=0.001 ) , and at 12 months ( 16 % , P=0.006 ) . Maximal VR was reduced 22 % ( P=0.001 ) at 2 weeks , 19 % ( P=0.001 ) at 6 months , and 14 % ( P=0.001 ) at 12 months . Sixteen of 51 patients on amiodarone and 4 of 52 on placebo converted to sinus rhythm during the study ( chi2=9.23 , P=0.002 ) . During follow-up , 11 of 268 patients in sinus rhythm on amiodarone at baseline and 22 of the 263 in sinus rhythm on placebo developed AF ; the difference was significant ( chi2=12.88 , P=0.005 ) . Analysis of total mortality during follow-up showed a significantly lower mortality rate ( P=0 . 04 ) in patients in AF at baseline who subsequently converted to sinus rhythm on amiodarone than in those who did not convert to sinus rhythm on the drug . CONCLUSIONS In patients with CHF , amiodarone has a significant potential to spontaneously convert patients in AF to sinus rhythm , with patients who convert having a lower mortality rate than those who do not . The drug prevented the development of new-onset AF and significantly reduced the VR in those with persistent AF OBJECTIVES This study evaluated the role of various clinical and echocardiographic parameters , including the left atrial appendage ( LAA ) antero grade flow velocity , for prediction of the long-term preservation of sinus rhythm  ( SR ) in patients with successful cardioversion ( CV ) of nonvalvular atrial fibrillation ( AF ) . BACKGROUND Echocardiographic parameters for assessing long-term SR maintenance after successful CV of nonvalvular AF are not accurately defined . METHODS Clinical , transthoracic echocardiographic and transesophageal echocardiographic ( TEE ) data --measured in AF lasting > 48 h -- of 186 consecutive patients ( 116 men , mean age : 65 + /- 9 years ) with successful CV ( electrical or pharmacologic ) were analyzed for assessment of one-year maintenance of SR . RESULTS At one-year follow-up , 91 of 186 ( 49 % ) patients who underwent successful CV continued to have SR . Mean LAA peak emptying flow velocity was higher in patients remaining in SR for one year than in those with AF relapse ( 41.7 + /- 20.2 cm/s vs. 27.7 + /- 17.0 cm/s ; p < 0.001 ) . On multivariate logistic regression analysis , only the mean LAA peak emptying velocity > 40 cm/s ( p = 0.0001 ; chi(2 ) : 23.9 , odds ratio [ OR ] = 5.2 , confidence interval [ CI ] 95 % = 2.7 to 10.1 ) and the use of preventive antiarrhythmic drug treatment ( p = 0.0398 ; chi(2 ) : 4.2 ; OR = 2.0 , CI 95 % = 1.0 to 3.8 ) predicted the continuous preservation of SR during one year , outperforming other univariate predictors such as absence of left atrial spontaneous echocardiographic contrast during TEE , the left atrial parasternal diameter < 44 mm , left ventricular ejection fraction > 46 % and AF duration < 1 week before CV . The negative and positive predictive values of the mean LAA peak emptying velocity > 40 cm/s for assessing preservation of SR were 66 % ( CI 95 % = 56.9 to 74.2 ) and 73 % ( CI 95 % = 62.4 to 83.3 ) , respectively . CONCLUSIONS In TEE-guided management of nonvalvular AF , high LAA flow velocity identifies patients with greater likelihood to remain in SR for one year after successful CV . Low LAA velocity is of limited value in identifying patients who will relapse into AF Objective Evaluation of efficacy of intravenous flecainide to revert supraventricular arrhythmias to sinus rhythm in patients with respiratory insufficiency . Design Comparative r and omized prospect i ve trial . Setting ICU in a University Hospital Patients 30 patients with acute respiratory insufficiency or acute exscerbation of chronic respiratory insufficiency and supraventricular arrhythmias .  Intravenous flecainide was administered to 15 patients ( Group A ) ( 2 mg/kg for 10 min and continuous perfusion of 1.5 mg/kg for 1 h ) . Intravenous verapamil was administered to 15 patients ( Group B ) ( 0.15 mg/kg for 5 min and continuous perfusion of 0.005 mg/kg/min for 1 h ) . Measurements and results The categories of patients ' arrhythmias were : Group A — atrial fibrillation ( AF ) in 5 cases , atrial flutter ( AFl ) in 2 , multifocal atrial tachycardia ( MAT ) in 4 and other supraventricular tachycardia ( SVT ) in 4 . Group B — AF in 6 cases , AFL in 2 , MAT in 2 and SVT in 5 cases . Flecainide  reverted arrhythmias to sinus rhythm in 12 out of 15 cases ( 80 % ) ; of these 12 , 11 reverted with the initial bolus . Verapamil reverted 5 out of 12 cases ( 33.3%,p<0.01 ) . No significant secondary adverse effects were detected . Conclusion Intravenous flecainide is an effective antiarrhythmic drug to treat acute supraventricular arrhythmias in patients with respiratory insufficiency In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine , 239 patients with paroxysmal atrial fibrillation were prospect ively treated with flecainide ( n = 122 ) or quinidine ( n = 117 ) in an open-label , r and omized trial . All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects . Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation ( difference , p = 0.282 ; not significant ) , fewer flecainide patients had to have their therapy discontinued due to adverse experiences ( p = 0.012 ) . Based on both endpoints ( efficacy and tolerability ) , an estimated 70.5 % of flecainide versus 55.4 % of quinidine patients would remain effectively treated at the end of 1 year on therapy ( p < or = 0.007 ) . The findings of this prospect i ve study suggest that in the treatment of paroxysmal atrial fibrillation ( 1 ) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation ; ( 2 ) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects ; and ( 3 ) given the overall endpoint of efficacy and tolerability , more patients are likely to continue long-term therapy with flecainide than with quinidine OBJECTIVES This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation . BACKGROUND Ibutilide fumarate is an intravenous ( IV ) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm . Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm . METHODS One hundred twenty-seven patients ( age range 22 to 92 years ) with atrial flutter or fibrillation of 3 h to 90 days ' ( mean 21 days ) duration were r and omized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate , separated by a 10-min infusion of 5 % dextrose in sterile water , or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride . RESULTS Of the 127 patients , 120 were evaluated for efficacy : 35 ( 58.3 % ) of 60 in the ibutilide group compared with 11 ( 18.3 % ) of 60 in the procainamide group had successful termination within 1.5 h of treatment ( p < 0.0001 ) . Seven patients were found to have violated the protocol and were not included in the final evaluation . In the patients with atrial flutter , ibutilide had a significantly higher success rate than procainamide ( 76 % [ 13 of 17 ] vs. 14 % [ 3 of 22 ] , p=0.001 ) . Similarly , in the atrial fibrillation group , ibutilide had a significantly higher success rate than procainamide ( 51 % [ 22 of 43 ] vs. 21 % [ 8 of 38 ] , p=0.005 ) . One patient who received ibutilide , which was found to be a protocol violation , had sustained polymorphic ventricular tachycardia requiring direct current cardioversion . Seven patients who received procainamide became hypotensive . CONCLUSIONS This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm .  Hypotension was the major adverse effect seen with procainamide . A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion BACKGROUND AND PURPOSE The optimal intensity of warfarin therapy for secondary prevention of stroke in nonvalvular atrial fibrillation ( NVAF ) remains unclear . We studied the efficacy and safety of conventional- and low-intensity warfarin therapy in a prospect i ve , r and omized , multicenter trial . METHODS The study population consisted of patients with NVAF ( < 80 years old ) who had a stroke or transient ischemic attack . The patients were r and omly allocated into a conventional-intensity group ( international normalized ratio [ INR ] 2.2 to 3.5 ) and a low-intensity group ( INR 1.5 to 2.1 ) . They were carefully monitored , and the annual rate of recurrent ischemic stroke and major hemorrhagic complications were compared between the groups . RESULTS We enrolled 115 patients ( mean age 66.7+/-6.5 years ) into the study . Fifty-five and 60 patients were allocated into the conventional- and low-intensity groups , respectively . The trial was stopped after a follow-up of 658+/-423 days , when major hemorrhagic complications occurred in 6 patients of the conventional-intensity group and the frequency ( 6.6 % per year ) was significantly higher than that in the low-intensity group ( 0 % per year , P=0.01 , Fisher 's exact test ) . All of the 6 patients with major bleeding were elderly ( mean age 74 years ) , and their mean  INR  before the major hemorrhage was 2.8 . The annual rate of ischemic stroke was low in both groups ( 1.1 % per year in the conventional-intensity group and 1.7 % per year in the low-intensity groups ) and did not differ significantly . CONCLUSIONS For secondary prevention of stroke in persons with NVAF , especially in old patients , the low-intensity warfarin ( INR 1.5 to 2 . 1 ) treatment seems to be safer than the conventional-intensity ( INR 2.2 to 3.5 ) treatment BACKGROUND Because atrial thrombi are poorly detected by conventional noninvasive techniques such as transthoracic echocardiography , patients with prolonged atrial fibrillation usually receive several weeks of oral anticoagulation therapy before cardioversion is attempted . We wondered whether transesophageal echocardiography , an accurate method of detecting atrial thrombi , would allow early cardioversion to be performed safely if no thrombi were identified . METHODS A total of 669 consecutive patients admitted with the diagnosis of atrial fibrillation were screened . Patients were excluded if they were receiving long-term anticoagulation , if the duration of atrial fibrillation was two days or less , if they were not c and i date s for cardioversion , or if transesophageal echocardiography was contraindicated . Of 119 qualifying patients , 94 agreed to participate ; the average duration of atrial fibrillation was 4.5 weeks . Participating patients underwent transthoracic echocardiography and transesophageal echocardiography followed by cardioversion if no thrombi were seen . Short-term anticoagulation with heparin was used in 80 patients before cardioversion , and 60 patients received warfarin for one month after cardioversion . RESULTS Fourteen atrial thrombi were identified in 12 patients ( 13 percent ) , and 12 of the 14 thrombi were visualized only on transesophageal echocardiography . Cardioversion was deferred in all 12 patients . Two of these 12 patients died suddenly ; 4 of the 10 surviving patients underwent uneventful cardioversion after prolonged oral anticoagulation . Seventy-eight of the 82 patients without thrombi underwent successful cardioversion to sinus rhythm ( 47 by means of antiarrhythmic drugs and 31 by electrical cardioversion ) , all without long-term oral anticoagulation . None of these patients ( 95 percent confidence interval , 0 to 4.6 percent ) had an embolic event . CONCLUSIONS In patients with atrial fibrillation of unknown or prolonged duration who are not receiving long-term anticoagulation , atrial thrombi are detected by transesophageal echocardiography in only a small minority ( 13 percent in our study ) . Our preliminary data suggest that if transesophageal echocardiography excludes the presence of thrombi , early cardioversion can be performed safely without the need for prolonged oral anticoagulation before the procedure The objective of this multicenter , r and omized , double-blind , placebo-controlled study was to determine the safety and efficacy of intravenous diltiazem in the treatment of 37 patients with rapid ( ventricular rate , mean + /- SD 142 + /- 17 beats/min ) atrial fibrillation or flutter and moderate to severe congestive heart failure ( ejection fraction , mean + /- SD 36 + /- 14 % ; New York Heart Association class III [ 23 patients ] , class IV [ 14 patients ] ) . During the double-blind portion of the study , patients received either intravenous diltiazem , 0.25 mg/kg over 2 minutes , or placebo followed 15 minutes later by diltiazem or placebo , 0.35 mg/kg over 2 minutes , if the first dose was tolerated but ineffective . Placebo nonresponders were given open-label intravenous diltiazem in a similar fashion as in the double-blind portion of the study . In the double-blind part of the study , 21 ( 18 with 0.25 mg/kg , 3 with an additional 0.35 mg/kg ) of the 22 patients ( 95 % ) responded to diltiazem , and 0 of 15 patients ( 0 % ) responded to placebo ( p < 0.001 ) . All 15 patients ( 13 with 0.25 mg/kg and 2 with an additional 0.35 mg/kg ) who received placebo during the double-blind period had a therapeutic response to diltiazem during open-label therapy . Overall , 36 of 37 patients ( 97 % ) had a therapeutic response to intravenous diltiazem .  Heart rate response to diltiazem after the 2-minute bolus infusions consisted of a > or = 20 % decrease in heart rate from baseline in 36 patients ; in addition , 17 patients also had heart rates decreased to < 100 beats/min , whereas no patient had conversion to sinus rhythm . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : We sought to assess the efficacy and safety of amiodarone for restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation in a prospect i ve , r and omized , double blind trial . Background : Restoration and preservation of sinus rhythm is difficult in patients with chronic atrial fibrillation . The efficacy of oral amiodarone has not been conclusively established . Methods : Ninety-five patients with chronic atrial fibrillation , lasting an average of 35.6 months , were r and omized to either amiodarone ( 600 mg/d ) ( 47 patients ) or placebo ( 48 patients ) during four weeks . Nonresponders underwent electric cardioversion , and those who reverted continued with amiodarone ( 200 mg/d ) or placebo . End-points were successful cardioversion and sinus rhythm maintenance . Results : Sixteen patients ( 34.04 % ) in the amiodarone group reverted within 27.28 ± 8.85 days in comparison with 0 % in the placebo group ( P < 0.000009 ) . The conversion rate rose to 51.72 % in patients with chronic atrial fibrillation lasting less than 12 months . Twenty-eight patients in the amiodarone group and 39 in the placebo group underwent electric cardioversion , which was successful in 19 patients ( 67.8 % ) of the amiodarone group and in 15 ( 38.46 % ) of the placebo group ( P = 0.017 ) . Altogether , conversion was obtained in 79.54 % of the amiodarone group patients and in 38.46 % of the placebo group patients ( P < 0.0001 ) . During follow-up , atrial fibrillation relapsed in 13 ( 37.14 % ) of 35 patients of the amiodarone group within 8.84 + 8.57 months and in 12 ( 80 % ; P = 0.009 ) of 15 patients of the placebo group within 2.74 ± 3.41 months . Conclusions : Oral amiodarone  restored sinus rhythm in one third of patients with chronic atrial fibrillation , increased the success rate of electric cardioversion , decreased the number of relapses and delayed their occurrence OBJECTIVES This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide , a pure class III antiarrhythmic agent , for the termination of sustained atrial fibrillation or flutter . BACKGROUND Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation . These effects , and preliminary clinical data , suggest that it may be effective in the treatment of atrial fibrillation and flutter . METHODS Ninety-one patients with sustained atrial fibrillation ( 75 patients ) or flutter ( 16 patients ) were entered into a double-blind , r and omized multicenter study of one of two doses of dofetilide ( 4 or 8 micrograms/kg body weight ) or placebo . RESULTS Dofetilide  effectively terminated the arrhythmia in 31 % of patients receiving 8 micrograms/kg , a statistically significant difference from those receiving 4 micrograms/kg ( conversion rate 12.5 % , p < 0.05 ) or placebo ( no conversion , p < 0.01 ) . Patients with atrial flutter had a greater response to dofetilide ( 54 % conversion rate ) than those with atrial fibrillation ( 14.5 % conversion rate , p < 0.001 ) . CONCLUSIONS Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm . However , its efficacy is greater in flutter -- a response that contrasts with the poorer response seen with class I agents . This finding potentially represents an important advance in the pharmacologic termination of atrial flutter In a placebo-controlled study the effects on ventricular rate regulation and exercise performance of xamoterol , 100 mg two times a day and 200 mg two times a day , and slow-release verapamil , 240 mg once a day , were assessed in 21 patients with chronic atrial fibrillation . The mean ventricular rate from noon to 6:00 PM was 101 + /- 20 beats/min with placebo , 95 + /- 17 beats/min with xamoterol 100 mg two times a day ( not significant ) , 90 + /- 16 beats/min with xamoterol 200 mg two times a day ( p less than 0.001 vs placebo ) and 78 + /- 19 beats/min with verapamil ( p less than 0.001 vs each other treatment ) . The mean ventricular rate from midnight to 6:00 AM was 69 + /- 16 beats/min with placebo , increased with xamoterol 100 mg two times a day and 200 mg two times a day to 75 + /- 15 beats/min and 74 + /- 16 beats/min , respectively ( p less than 0.001 vs placebo ) , but decreased with verapamil to 62 + /- 15 beats/min ( p less than 0.001 vs each other treatment ) . The number of ventricular pauses greater than 2.0 seconds was increased by verapamil ( p less than 0.05 ) . All active treatments reduced exercise ventricular rates ( p less than 0.001 ) , but the decrease was more pronounced with verapamil . The anaerobic threshold was reached significantly earlier with verapamil than with placebo ( 72 + /- 32 W vs 79 + /- 37 W ; p less than 0.01 ) . Xamoterol is preferable to verapamil for treatment of patients with chronic atrial fibrillation who exhibit both bradycardia at rest and excessive tachycardia during exercise . ( ABSTRACT TRUNCATED AT 250 WORDS Background Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke . Methods and Main Results . The Stroke Prevention in Atrial Fibrillation Study , a multicenter , r and omized trial , compared 325 mg/day aspirin ( double-blind ) or warfarin with placebo for prevention of ischemic stroke and systemic embolism ( primary events ) , and included 1,330 in patients and out patients with constant or intermittent atrial fibrillation . During a mean follow-up of 1.3 years , the rate of primary events in patients assigned to placebo was 6.3 % per year and was reduced by 42 % in those assigned to aspirin ( 3.6 % per year , p = 0.02 ; 95 % confidence interval , 9–63 % ) . In the subgroup of  warfarin-eligible patients ( most less than 76 years old ) , warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67 % ( warfarin versus placebo , 2.3 % versus 7.4 % per year , p = 0.01 ; 95 % confidence interval , 27–85 % ) . Primary events or death were reduced 58 % ( p = 0.01 ) by warfarin and 32 % ( p = 0.02 ) by aspirin . The risk of significant bleeding was 1.5 % , 1.4 % , and 1.6%o per year in patients assigned to warfarin , aspirin , and placebo , respectively . Conclusions Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation . Because warfarin-eligible patients composed a subset of all aspirin-eligible patients , the magnitude of reduction in events by warfarin versus aspirin can not be compared . Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin , and the trial is continuing to address this issue . Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke In a controlled study comprising 176 patients ,  quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation  during a 1-year follow-up period after successful electric shock conversion . After one year , 51 per cent ( 52/101 ) of the patients in the quinidine group , and 28 per cent ( 21/75 ) in the control group remained in sinus rhythm ( P smaller than 0.001 ) . No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion . Gastrointestinal side-effects were not uncommon , and caused interruption of quinidine treatment in some cases The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias . In our double‐blind , r and omized , parallel , multiclinic study , subjects received timolol , 1 mg iv , or matching placebo as a starting dose , followed by a second and third dose of 1 mg each ( or matching placebo ) at 20‐min intervals if the arrhythmia did not convert to sinus rhythm . Subjects in whom the sinus rhythm returned or the ventricular rate decreased to < 100 bpm were transferred to a dosing regimen of timolol in 10‐mg tablets twice a day by mouth , 1 hr after the last intravenous dose . Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo . The overall proportion of responders ( either conversion to sinus rhythm or a decrease in ventricular rate to < 100 bpm ) was 68 % after timolol and 7 % after placebo . The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia ( 26 of 32 subjects and two of 38 subjects ) , atrial fibrillation ( 17 of 29 subjects and three of 32 subjects ) , and atrial flutter ( seven of 11 subjects and one of nine subjects ) . The most common adverse effects were bradycardia and hypotension We evaluated the effectiveness of oral verapamil therapy for control of ventricular rate in digitalized patients with atrial fibrillation ( AF ) with three clinical problems : chronic AF with rapid rate at rest ( four patients ) , chronic AF with accelerated rate during modest exercise ( five patients ) , and rapid rates during paroxysmal AF ( four patients ) . Patients in the first two categories were evaluated both by open-label dosage titration and by a r and omized , double-blind , cross-over protocol . In chronic AF with rapid rate of rest , there was a significant reduction in resting heart rate ( from 125 + /- 7 to 87 + /- 14 , P less than 0.01 ) and in peak exercise heart rate ( from 162 + /- 33 to 126 + /- 25 , P less than 0.01 ) . In chronic AF with rapid rate during exercise , there was also a significant decrease in resting heart rate ( from 90 + /- 7 to 66 + /- 4 , P less than 0.01 ) and in peak exercise heart rate ( from 126 + /- 19 to 101 + /- 15 , P less than 0.01 ) . These effects continued during longterm follow-up of one to 12 months ( mean seven months ) . In patients with paroxysmal AF , verapamil slowed the ventricular response from 16- + /- 24 to 72 + /- 4 P less than 0.01 ) with only some amelioration of symptoms . Therapy was well tolerated despite a high prevalence ( seven of 13 patients ) of radiographic cardiomegaly ( cardiothoracic ratio greater than 0.55 ) . We conclude that verapamil is a safe and useful drug for control of ventricular rate in digitalized patients with chronic and paroxysmal AF Summary This open , parallel-group , multicenter study was conducted to compare the efficacy and safety of sotalol with that of quinidine for the prevention of  atrial fibrillation relapse following DC conversion 183 . DC-converted 183 patients with a 1- to 12-month history of atrial fibrillation were r and omized to sotalol or quinidine after 2 hours of sinus rhythm following the conversion and followed on treatment for 6 months . The efficacy of  sotalol  and quinidine for the prevention of atrial fibrillation relapse during a 6-month period following DC conversion was similar . However , sotalol  was better tolerated than quinidine Patients with atrial fibrillation frequently show a wide variation in heart rate with digoxin therapy . We have compared the effect on heart rate variability , of doubling the digoxin dosage or adding verapamil 120 mg daily in a r and omized cross-over study in 14 patients . Twenty-four hour ambulatory electrocardiographic recordings , six minute walking tests and palpitation and breathlessness scores were obtained on each regime . All patients exhibited a diurnal pattern in  heart rate variability . Both treatments significantly lowered heart rate but high dose digoxin lowered minimum heart rate significantly more than digoxin and verapamil , causing more night time bradycardia . Overall , digoxin with verapamil produced significantly less heart rate variability than digoxin alone . Day time but not night time pauses were prolonged by digoxin and verapamil but were prolonged more by high dose digoxin . Five ( 36 % ) patients had serum digoxin levels in the toxic range when taking high dose digoxin .  Palpitations were significantly reduced by both treatments but most improvement occurred with digoxin and verapamil . No significant effect was found on six minute walking distances or breathlessness scores . In conclusion , the addition of verapamil to digoxin was superior to increasing the dose of digoxin alone , producing significantly better control of heart rate variability with less night time bradycardia In a single-blind r and omized study , the efficacy of intravenous flecainide ( 2 mg/kg/10 minutes ) versus verapamil ( 10 mg/1 minute ) was assessed in 40 patients with paroxysmal atrial fibrillation ( AF ) or atrial flutter ( AFI ) . The treatment was considered successful if sinus rhythm occurred within 1 hour . Of 20 patients receiving flecainide , 14 of 17 ( 82 % ) with AF converted to sinus rhythm , but in 3 patients with AFI flecainide failed . All patients treated with verapamil ( 17 AF , 3 AFI ) showed lower ventricular rates after 1 hour ; however , only 1 ( 6 % ) with AF converted to sinus rhythm and 1 ( 6 % ) converted to AFI . Patients who did not convert to sinus rhythm after treatment with verapamil were treated with flecainide and observed for another hour . After the change to flecainide , 9 of 15 patients ( 60 % ) with AF still converted . Thus , 23 of 32 patients ( 72 % ) with AF and none of 7 with AFI converted to sinus rhythm after treatment with flecainide .  Conversion to sinus rhythm was achieved in 19 of 22 patients ( 86 % ) when AF lasted less than 24 hours and in 4 of 10 ( 40 % ) when the arrhythmia lasted greater than 24 hours . Transient adverse effects were noted in 10 patients ( 26 % ) after flecainide . In summary , flecainide is an effective and safe drug for conversion of paroxysmal AF to sinus rhythm , but ineffective for AFI . Verapamil appears to be of no use for conversion of AF or AFI to sinus rhythm The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . BACKGROUND AND PURPOSE The results of a large prospect i ve r and omized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation ( NRAF ) ; less well established is the role of antiplatelet agents . The present study compared the effects of indobufen , a reversible inhibitor of platelet cyclooxygenase , with those of warfarin in this setting . METHODS A total of 916 patients with NRAF and a recent ( < or = 15 days ) cerebral ischemic episode were admitted to this multicenter , r and omized study , during which they were treated with either indobufen ( 100 or 200 mg BID ) or warfarin ( to obtain an international normalized ratio of 2.0 to 3.5 ) for 12 months . The two groups ( 462 on indobufen and 454 on warfarin ) were well balanced in terms of their main baseline characteristics . The primary outcome of the study was the combined incidence of nonfatal stroke ( including intracerebral bleeding ) , pulmonary or systemic embolism , nonfatal myocardial infa rct ion , and vascular death . RESULTS At the end of follow-up , the incidence of primary outcome events was 10.6 % in the indobufen group ( 95 % confidence interval , 7.7 % to 13.5 % ) and 9.0 % in the warfarin group ( 95 % confidence interval , 6.3 % to 11.8 % ) , with no statistically significant difference between treatments . The frequency of noncerebral major bleeding complications was low : only four cases ( 0.9 % ) of gastrointestinal bleeding were observed , all of them in the warfarin group . CONCLUSIONS We conclude that , within the limitations of its design , this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment One hundred patients were subjected to a controlled study of the effectiveness of quinidine treatment upon the maintenance of sinus rhythm after electroconversion .  The quinidine series was treated with a long-acting preparation of quinidine sulphate , which was given in a dosage to achieve serum levels between 4 and 6 mg/l . The control series received no quinidine . The maintenance rate did not differ significantly in the two series during the first three months , but for the remaining observation time until I2 months a sigmficant difference in favour of quinidine was present . Identical results were found in a cross-over experiment , in which 24 patients served as their own controls . Further analysis broughtforward that quinidine was effective only if the atrial fibrillation had lasted for less than one year before electroconversion . Complications due to STUDY OBJECTIVES To investigate the efficacy and safety of amiodarone administered as the drug of first choice in the conversion of atrial fibrillation , regardless of its duration . DESIGN : Prospect i ve , r and omized , controlled clinical study . SETTING : Tertiary cardiac referral center . PATIENTS Two-hundred eight consecutive patients ( 102 men ; mean [ + /- SD ] age , 65 + /- 10 years ) with atrial fibrillation . INTERVENTIONS One-hundred eight patients received amiodarone , and 100 patients received placebo treatment . Patients r and omized to amiodarone received 300 mg IV for 1 h , and then 20 mg/kg for 24 h. They were also given 600 mg/d orally , divided into three doses , for 1 week , and thereafter 400 mg/d for 3 weeks . Patients r and omized to placebo treatment received an identical amount of saline solution IV over 24 h , and oral placebo treatment for 1 month . MEASUREMENTS AND RESULTS Baseline clinical characteristics were similar in the two groups . Conversion to sinus rhythm was achieved in 87 of 108 patients ( 80.05 % ) who received amiodarone , and in 40 of 100 patients ( 40 % ) in the placebo group ( p < 0.0001 ) . Statistical analysis showed that the duration of the arrhythmia and the size of the left atrium affected both the likelihood of conversion to sinus rhythm and the time to conversion in both groups . No side effects requiring discontinuation of treatment were observed in either group . CONCLUSIONS Amiodarone appears to be safe and effective in the termination of atrial fibrillation . However , extreme cases with a large left atrium and long-lasting arrhythmia need long-term therapy Ninety-two patients were entered in a double-blind controlled trial of long-acting quinidine bisulphate for the maintenance of sinus rhythm following DC reversion of atrial fibrillation . By r and om selection two statistically comparable groups of patients were obtained , a control group being given a placebo and a treated group quinidine bisulphate 1.5 g. per day in two 12-hourly doses . Thirty-seven patients were followed up in the control group and twenty-eight patients in the treated group . The maintenance of sinus rhythm in the treated group was significantly longer than in the control group , especially during the first three months . The mean serum quinidine level in the treated group was 2.2+/-0.3 ( SEM ) mg . per litre . There was one death among the patients treated with quinidine , which may have been due to quinidine toxicity caused by a high serum quinidine level In 39 patients undergoing electrical cardioversion for atrial fibrillation ( AF ) , we examined the effect of total electrical energy used for cardioversion on postcardioversion peak left atrial ( LA ) rapid filling velocity ( A ) and the atrial emptying fraction , and recovery of LA effective mechanical atrial function ( defined as peak A velocity > or = 0.50 m/s ) , as assessed by transthoracic echocardiography . In a subset of 27 patients who underwent pre- and postcardioversion transesophageal echocardiography  , we assessed the relation between total electrical energy and LA appendage filling and emptying velocities and spontaneous echo contrast . Patients were r and omized to receive an initial shock of 1.5 J/kg based on body weight , or 2.5 , 3.5 , 5 J/kg , or 360 J , followed sequentially by higher shock intensities until sinus rhythm was achieved . Patients were classified into 4 groups based on quartiles of total energy delivered for cardioversion . Conversion to sinus rhythm was associated with a significant decrease in the LA appendage filling velocities ( 0.42 + /- 0.20 m/s vs 0.29 + /- 0.14 m/s ; p = 0.002 ) and LA appendage emptying velocities ( 0.40 + /- 0.22 m/s vs 0.29 + /- 0.18 m/s ; p = 0.03 ) , but no change in the incidence of spontaneous echo contrast ( 61 % vs 70 % , p = 0.08 ) . The 4 groups of patients did not differ with respect to postcardioversion LA appendage filling velocities , LA appendage emptying velocities , incidence of spontaneous echo contrast , or worsening of spontaneous echo contrast . Similarly , the change in LA appendage filling and emptying velocities associated with cardioversion was not different between the groups . Furthermore , postcardioversion peak A velocity and atrial emptying fraction and recovery of effective mechanical atrial function were similar between the 4 groups . These results suggest that in patients undergoing electrical cardioversion for AF , the total electrical energy used for cardioversion has no effect on the mechanical function of the left atrium or LA appendage following cardioversion Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON  Dofetilide  ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P < 0.001 ) . Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P < 0.0001 ) . In addition , dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival OBJECTIVE To investigate whether an oral loading dose of flecainide is as safe and effective as intravenous flecainide for the cardioversion of acute atrial fibrillation . DESIGN Prospect i ve , r and omised , double blind , double placebo study . SETTING Cardiac care unit of a large district general hospital in the UK . PATIENTS AND METHODS 79 patients presenting with symptomatic acute atrial fibrillation : patients were given either intravenous flecainide ( n = 39 ) or a solution of oral flecainide ( n = 40 ) , with appropriate placebos . All patients were heparinised during the study . PRIMARY OUTCOME MEASURES Safety ; mean time to cardioversion ; proportion of patients restored to sinus rhythm at two hours and eight hours after treatment . Analysis was by intention to treat . RESULTS There were no differences in baseline characteristics between the oral and intravenous groups . Both forms of flecainide were well tolerated , with no adverse clinical events during the study . The mean time to cardioversion was 110 minutes in the oral group and 52 minutes in the intravenous group ( p = 0.002 ) . Two hours after treatment , 27 of the 40 patients in the oral group ( 68 % ) and 25 of the 39 in the intravenous group ( 64 % ) had reverted to sinus rhythm ( p = 0.74 ) . Eight hours after treatment , 30 patients in the oral group ( 75 % ) and 28 in the intravenous group ( 72 % ) had reverted to sinus rhythm ( p = 0.76 ) . CONCLUSIONS Intravenous flecainide restored sinus rhythm more rapidly than oral flecainide , but at two hours and eight hours after treatment there was no difference in the proportion of patients cardioverted by the two approaches . These results suggest a role for oral loading doses of flecainide in the treatment of acute or symptomatic paroxysmal atrial fibrillation AIMS This study compared the efficacy and safety of intravenous dofetilide with amiodarone and placebo in converting atrial fibrillation or flutter to sinus rhythm . METHODS AND RESULTS One hundred and fifty patients with atrial fibrillation or flutter ( duration range 2 h-6 months ) were given 15-min intravenous infusions of 8 microg . kg(-1)of dofetilide ( n=48 ) , 5 mg . kg(-1)of amiodarone ( n=50 ) , or placebo ( n=52 ) and monitored continuously for 3 h. Sinus rhythm was restored in 35 % , 4 % , and 4 % of patients , respectively ( P<0.001 , dofetilide vs placebo;P = ns , amiodarone versus placebo ) . Dofetilide was more effective in atrial flutter than in atrial fibrillation ( cardioversion rates 75 % and 22 % , respectively;P=0.004 ) . The mean time to conversion with dofetilide was 55+/-15 min . Dofetilide prolonged the QTc interval ( + 16 % at 20 min ) . Amiodarone substantially decreased the ventricular rate in non-converters ( -18 beats . min(-1)at 30 min ) . Two patients given dofetilide ( 4 % ) had non-sustained ventricular tachycardias , and four ( 8 % ) had torsade de pointes , in one case requiring electrical cardioversion . CONCLUSION Intravenous dofetilide is significantly more effective than amiodarone or placebo in restoring sinus rhythm in patients with atrial fibrillation or flutter . However , when infused intravenously at this dose and rate , dofetilide causes a significant incidence of torsade de pointes BACKGROUND Clinical studies have shown that biphasic shocks are more effective than monophasic shocks for ventricular defibrillation . The purpose of this study was to compare the efficacy of a rectilinear biphasic waveform with a st and ard damped sine wave monophasic waveform for the transthoracic cardioversion of atrial fibrillation . METHODS AND RESULTS In this prospect i ve , r and omized , multicenter trial , patients undergoing transthoracic cardioversion of atrial fibrillation were r and omized to receive either damped sine wave monophasic or rectilinear biphasic shocks .  Patients r and omized to the monophasic protocol ( n=77 ) received sequential shocks of 100 , 200 , 300 , and 360 J. Patients r and omized to the biphasic protocol ( n=88 ) received sequential shocks of 70 , 120 , 150 , and 170 J. First-shock efficacy with the 70-J biphasic waveform ( 60 of 88 patients , 68 % ) was significantly greater than that with the 100-J monophasic waveform ( 16 of 77 patients , 21 % , P<0.0001 ) , and it was achieved with 50 % less delivered current ( 11+/-1 versus 22+/-4 A , P<0.0001 ) . Similarly , the cumulative efficacy with the biphasic waveform ( 83 of 88 patients , 94 % ) was significantly greater than that with the monophasic waveform ( 61 of 77 patients , 79 % ; P=0.005 ) . The following 3 variables were independently associated with successful cardioversion : use of a biphasic waveform ( relative risk , 4.2 ; 95 % confidence intervals , 1.3 to 13.9 ; P=0.02 ) , transthoracic impedance ( relative risk , 0.64 per 10-Omega increase in impedance ; 95 % confidence intervals , 0.46 to 0.90 ; P=0.005 ) , and duration of atrial fibrillation ( relative risk , 0.97 per 30 days of atrial fibrillation ; 95 % confidence intervals , 0.96 to 0.99 ; P=0.02 ) . CONCLUSIONS For transthoracic cardioversion of atrial fibrillation , rectilinear biphasic shocks have greater efficacy ( and require less energy ) than damped sine wave monophasic shocks UNLABELLED This r and omized study compared the efficacy and safety of amiodarone , propafenone and sotalol in the prevention of atrial fibrillation . METHODS The population consisted of 214 consecutive patients ( mean age 64 + /- 8 years , 106 men ) with recurrent symptomatic atrial fibrillation . After restoration of sinus rhythm , patients were r and omized to amiodarone ( 200 mg/day ) , propafenone ( 450 mg/day ) or sotalol ( 320 + /- 20 mg/day ) . Follow-up evaluations were conducted at 1 , 2 , 4 and 6 months , and at 3-month intervals thereafter . The proportion of patients developing recurrent atrial fibrillation and /or experiencing unacceptable adverse effects was measured in the three groups by the Kaplan-Meier method . RESULTS Recurrent atrial fibrillation occurred in 25 of the 75 patients treated with amiodarone compared to 51 of the 75 patients treated with sotalol and 24 of the 64 patients treated with propafenone . Fourteen patients treated with amiodarone , five with sotalol , and one with propafenone experienced adverse effects while in sinus rhythm , necessitating discontinuation of treatment ( P < 0.001 for amiodarone and propafenone vs sotalol ) . The difference between amiodarone and propafenone was statistically nonsignificant when all events were included in the analysis . However , if the analysis was limited to recurrent atrial fibrillation events , amiodarone was more effective than propafenone ( P < 0.05 ) . CONCLUSIONS Amiodarone and propafenone were superior to sotalol in maintaining long-term normal sinus rhythm in patients with atrial fibrillation .  Amiodarone tended to be superior to propafenone , though its long-term efficacy was limited by adverse side effects The safety and efficacy of oral verapamil to control exercise tachycardia in 27 patients with atrial fibrillation and 3 with atrial flutter receiving digitalis was evaluated in a double-blind , r and omized , crossover study . The heart rate in patients who received verapamil compared with placebo group was lower at rest ( mean 69 + /- 13 versus 87 + /- 20 beats/min , p less than 0.01 ) , as was the degree of tachycardia at the end of 3 minutes of a st and ardized exercise test ( 104 + /- 14 versus 136 + /- 23 beats/min , p less than 0.01 ) . Doses of verapamil required to achieve suppression of tachycardia were 240 mg/day in 18 patients , 320 mg/day in 6 patients , and 480 mg/day in 3 patients . Only 3 patients complained of adverse effects from verapamil during the double-blind phase of the study . Two patients were discontinued from the study because of adverse reactions . No clinical ly significant changes during verapamil therapy were observed on the electrocardiogram , chest roentgenogram , echocardiogram or in the laboratory evaluation . Digoxin blood levels were higher in patients who received concomitant verapamil compared with placebo ( 1.23 + /- 0.59 versus 0.85 + /- 0.46 ng/ml , p less than 0.01 ) , but no patient had signs or symptoms of digitalis toxicity . Thus , oral verapamil given in addition to digitalis is a safe and effective agent in the treatment of patients with chronic atrial fibrillation or flutter to decrease exercise-induced tachycardia BACKGROUND Few antiarrhythmic agents have been shown in r and omized controlled trials to be effective and well tolerated in the prophylaxis of paroxysmal supraventricular tachycardia or paroxysmal atrial fibrillation .  Propafenone , a class IC anti-arrhythmic agent with weak beta-adrenoceptor antagonist properties , has shown promise in preliminary clinical studies . METHODS AND RESULTS A double-blind , placebo-controlled trial of the efficacy and tolerability of propafenone was undertaken in 100 patients with paroxysmal supraventricular tachycardia ( [ PSVT ] n = 52 ) or atrial fibrillation/flutter ( [ PAF ] n = 48 ) who had recorded two or more symptomatic arrhythmia recurrences by transtelephonic ECG monitoring during a 3-month drug-free observation period . Patients were r and omized into two consecutive crossover periods of propafenone ( 300 mg BID ) versus placebo followed by 300 mg TID propafenone versus placebo . Analysis was based on the time to treatment failure , defined as the interval from treatment onset to the occurrence of either ECG-documented arrhythmia or an intolerable adverse event . With a proportional-hazards model , we determined the relative risk ( 95 % confidence interval ) of treatment failure after the achievement of steady-state drug levels for placebo compared with propafenone 300 mg BID to be 6.8 ( 2.2 to 21.2 , P < .001 , n = 45 ) for PSVT and 6.0 ( 1.8 to 20.0 , P = .004 , n = 30 ) for PAF . Due to a greater incidence of adverse events on high-dose propafenone , the relative risks of receiving placebo rather than propafenone 300 TID were only 2.2 ( 0.9 to 5.3 , P = .1 , n = 34 ) for PSVT and 1.9 ( 0.7 to 4.7 , P = .2 , n = 25 ) for PAF . However , if adverse events were excluded in the high-dose comparison , relative risks for arrhythmia recurrence were 15.0 ( 2.0 to 113 , P = .009 ) for PSVT and incalculable ( no preferences for placebo , P = .0002 ) for PAF . One episode of wide-complex tachycardia was documented during propafenone therapy . CONCLUSIONS Propafenone is of value in the prophylaxis of both PSVT and PAF . A dose of 300 mg BID is effective and well tolerated . A larger dose of 300 mg TID causes more adverse effects but may be more effective in those who can tolerate it BACKGROUND Despite the efficacy of warfarin sodium therapy for stroke prevention in atrial fibrillation , many physicians hesitate to prescribe it to elderly patients because of the risk for bleeding complications and because of inconvenience for the patients . METHODS The Second Copenhagen Atrial Fibrillation , Aspirin , and Anticoagulation Study was a r and omized , controlled trial examining the following therapies : warfarin sodium , 1.25 mg/d ; warfarin sodium , 1.25 mg/d , plus aspirin , 300 mg/d ; and aspirin , 300 mg/d . These were compared with adjusted-dose warfarin therapy ( international normalized ratio of prothrombin time [ INR ] , 2.0 - 3.0 ) . Stroke or a systemic thromboembolic event was the primary outcome event . Transient ischemic attack , acute myocardial infa rct ion , and death were secondary events . Data were h and led as survival data , and risk factors were identified using the Cox proportional hazards model . The trial was scheduled for 6 years from May 1 , 1993 , but due to scientific evidence of inefficiency of low-intensity warfarin plus aspirin therapy from another study , our trial was prematurely terminated on October 2 , 1996 . RESULTS We included 677 patients ( median age , 74 years ) . The cumulative primary event rate after 1 year was 5.8 % in patients receiving minidose warfarin ; 7.2 % , warfarin plus aspirin ; 3.6 % , aspirin ; and 2.8 % , adjusted-dose warfarin ( P = .67 ) . After 3 years , no difference among the groups was seen . Major bleeding events were rare . CONCLUSIONS Although the difference was insignificant , adjusted-dose warfarin seemed superior to minidose warfarin and to warfarin plus aspirin after 1 year of treatment . The results do not justify a change in the current recommendation of adjusted-dose warfarin ( INR , 2.0 - 3.0 ) for stroke prevention in atrial fibrillation Six patients with chronic atrial fibrillation ( AF ) took single doses of digoxin , verapamil and diltiazem , alone and in combination . Three hours after dosing , resting and post-exercise heart rate , exercise tolerance and resting and post-exercise cardiac output were measured . Post-exercise heart rates ranged from 167 bpm ( after placebo ) to 122 bpm ( after digoxin plus diltiazem ) ( P less than 0.05 ) . However , the lower ventricular rates seen after treatment with the calcium antagonists were not associated with improved exercise tolerance , which did not differ significantly between the various treatments . Reduction of the ventricular rate was associated with a small increase in stroke volume but the benefits of this were offset by a rate related reduction in cardiac output . Further reduction of the rapid ventricular rates seen in digitalized patients with AF does not appear to be of benefit in terms of improving either exercise tolerance or cardiac output OBJECTIVES This study was design ed to determine the efficacy of intravenous amiodarone in the management of  recent-onset atrial fibrillation .  BACKGROUND The optimal approach for acute atrial fibrillation has not been established . Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias , but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated . METHODS Sample size was calculated to detect a 25 % increase in reversion rate with amiodarone with a statistical power of 80 % . One hundred consecutive patients with recent-onset ( < 1 week ) atrial fibrillation and not taking antiarrhythmic agents were r and omized to receive either intravenous amiodarone , 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h , or an identical amount of saline . Both groups received intravenous digoxin , 0.5 mg initially , followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter , to complete 24 h while the ventricular rate was > 100 beats/min . Amiodarone and digoxin  blood levels were determined . Both groups were homogeneous regarding underlying heart disease , time from onset to treatment , initial ventricular rate and left atrial size . RESULTS By the end of the 24-h treatment period , 34 patients ( 68 % , 95 % confidence interval [ CI ] 53 % to 80 % ) in the amiodarone group and 30 ( 60 % , 95 % CI 45 % to 74 % ) in the control group had returned to sinus rhythm ( p = 0.532 ) . Mean times ( + /-SD ) of conversion were 328 + /- 335 and 332 + /- 359 min , respectively ( p = 0.957 ) . Among patients who did not convert to sinus rhythm , treatment with amiodarone was associated with a slower ventricular rate ( 82 + /- 15 beats/min in the amiodarone group vs. 91 + /- 23 beats/min in the control group , p = 0.022 ) . After restoration of sinus rhythm , atrial fibrillation recurred during a 15-day follow-up period in 4 ( 12 % ) of 34 patients ( 95 % CI 3 % to 27 % ) in the amiodarone group and in 3 ( 10 % ) of 30 ( 95 % CI 2 % to 26 % ) in the control group ( p = 0.861 ) . CONCLUSIONS Intravenous amiodarone , at the doses used in this study , produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm STUDY OBJECTIVES The objectives of this study were to assess the efficacy of parenteral magnesium sulfate ( MgSO4 ) , digoxin , and combined MgSO4-digoxin therapies in acutely lowering ventricular rates in patients with newly recognized atrial fibrillation . DESIGN A r and omized , double-blinded , placebo-controlled clinical study . SETTING US Army tertiary care facility . PARTICIPANTS Fifteen adults ( mean age , 62 + /- 19 years ) presenting with newly recognized atrial fibrillation and rapid ventricular rate ( more than 99 ) . INTERVENTIONS Patients were given an initial parenteral MgSO4 bolus with continuous infusion or placebo . After 30 minutes , all patients were given 0.5 mg IV digoxin and followed for 3.5 hours . MEASUREMENTS AND MAIN RESULTS Ventricular rates were obtained at baseline , every 5 minutes for the first 30 minutes , and then every 30 minutes for 3.5 hours . At 5 minutes , ventricular rates decreased 16 + /- 7 % ( P < .02 ) with MgSO4 ; this was comparable with rate control with digoxin ( 18 + /- 9 % ) at 4 hours . Rate control tended ( 26 + /- 7 % ) to improve with combined therapy . CONCLUSION Parenteral MgSO4 may be useful in the acute management of rapid ventricular rates in patients with atrial fibrillation BACKGROUND Atrial fibrillation ( AF ) is associated with impaired exercise capacity . Oxygen uptake ( VO2 ) kinetics determines cardiopulmonary performance during submaximal exercise , which may be impaired in patients with AF . AIM To study oxygen kinetics and cardiopulmonary performance in patients with AF without structural heart disease and the effects of oral sotalol on these parameters . PATIENTS AND METHODS Twenty consecutive patients ( mean age , 56+/-8 years ) with chronic AF were recruited . The protocol design was a r and omized , single-blinded , and placebo-controlled trial . Patients received either sotalol or placebo for an 8-week study period , and the alternative treatment in the subsequent period .  Cardiopulmonary function tests  using constant workload and incremental workload protocol s were performed at the end of each phase . Sixteen age-matched normal subjects were included as control subjects . RESULTS During constant submaximal exercise , patients with AF had a larger oxygen deficit ( 425+/-140 mL vs 289+/-80 mL in normal subjects ; p<0.05 ) and the time for achieving 63 % of VO2 ( mean response time ) was also delayed ( 46+/-15 s vs 33+/-10 s ; p<0.05 ) . Compared with normal subjects , patients with chronic AF had a higher maximal exercise heart rate ( 180+/-34 beats/min vs 153+/-22 beats/min ; p<0.05 ) , but a lower maximal VO2 ( 20+/-4 mL/kg/min vs 26+/-6 mL/kg/min ; p<0.05 ) . Oral sotalol lowered the resting ( 72+/-15 beats/min vs 93+/-22 beats/min ; p<0.05 ) and exercise heart rate compared with placebo ( 125+/-27 beats/min vs 180+/-34 beats/min ; p<0.05 , respectively ) , and normalized oxygen pulse and the heart rate to minute ventilation ratio during maximal exercise . There was no significant difference between those receiving sotalol and those receiving placebo in oxygen deficit ( 502+/-150 mL vs 425+/-140 mL ; p=0.38 ) , maximal VO2 ( 17.2+/-4.9 mL/kg/min vs 20.4+/-4.7 mL/kg/min ; p=0.17 ) , and other gas exchange variables . In patients with AF , oxygen deficit has a fair correlation with VO2 at the anaerobic threshold ( r2=0.43 ; p<0.05 ) and at maximal exercise ( r2=0.45 ; p<0.05 ) . CONCLUSION In addition to maximal exercise capacity and cardiopulmonary performance , patients with chronic AF without significant structural heart disease had impaired submaximal exercise performance as assessed by VO2 kinetics . These parameters were not significantly affected by sotalol used for rate control Efficacy and safety of intravenous flecainide ( 2 mg/kg body weight in 10 minutes ) , verapamil ( 10 mg in 1 minute ) , and propafenone ( 2 mg/kg body weight in 10 minutes ) were investigated in 90 consecutive patients with atrial fibrillation ( AF ) or flutter ( AFL ) . In the first 40 patients , flecainide and verapamil were evaluated ; in the second 50 patients , flecainide and propafenone were compared , both in a single-blind r and omized study design . The primary end point was sinus rhythm occurring within 1 hour after start of infusion . Sinus rhythm was attained in 32 of 37 patients ( 86 % ) with AF treated with flecainide and in 11 of 20 patients ( 55 % ) with AF treated with propafenone . In recent onset AF ( less than or equal to 24 hours ) conversion rates were 24 of 25 patients ( 96 % ) in the flecainide group and 8 of 14 patients ( 57 % ) in the propafenone group ( p less than 0.05 ) . Conversion of AFL occurred in only 1 of 8 patients ( 13 % ) in the flecainide-treated patients and in 2 of 5 patients ( 40 % ) treated with propafenone ( difference not significant ) . Verapamil was almost ineffective , since only 1 of 20 patients ( 5 % ) responded within 1 hour . Time to conversion was 21 + /- 17 minutes in the flecainide group and 16 + /- 10 minutes in the propafenone group . QRS widening occurred in flecainide-treated patients ( 83 + /- 15 to 99 + /- 20 msec ; p less than 0.001 ) , but not after propafenone ( 83 + /- 11 to 86 + /- 12 msec ) . Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone . ( ABSTRACT TRUNCATED AT 250 WORDS UNLABELLED The aim of the study was to investigate the efficacy of diltiazem bolus intravenous administration , compared to disopyramide , in the treatment of various types of paroxysmal supraventricular tachyarrhythmias . METHOD Fifty patients ( 23 males , 27 females , mean age 47.7 + /- 15.2 years ) with paroxysmal supraventricular tachyarrhythmia ( 20 with paroxysmal atrial tachycardia , 23 with paroxysmal atrial fibrillation and rapid ventricular response and 7 with atrial fluttering ) were studied . Diltiazem at a dose of 0.25 - 0.30 mg/kg BW or disopyramide at a dose of 50 mg were given bolus IV . If conversion of the arrhythmia to sinus rhythm could not be achieved with the initial drug , the alternate was given . The order of administration of the drugs was r and om , independent of the type of the arrhythmia . Before and during drug administration detailed clinical examination and frequent blood pressure ( BP ) measurements were performed . Twenty-four hour Holter monitoring was done in all patients , starting with the administration of the antiarrhythmic drug . RESULTS 1 ) Paroxysmal atrial tachycardia : diltiazem administration converted the arrhythmia to sinus rhythm in all patients while disopyramide in only 1 of 9 patients who received this drug . 2 ) Paroxysmal atrial fibrillation : disopyramide converted the arrhythmia in 5 patients without significant change in ventricular response in the others . Diltiazem did not convert the arrhythmia though it caused significant decrease in ventricular response ( < 100 bpm ) and in 1 patient an important bradycardia ( 45 bpm ) . 3 ) Atrial fluttering : disopyramide converted the arrhythmia to sinus rhythm in 1 patient without significant change in the ventricular response in the others . Diltiazem caused significant decrease in the ventricular response without conversion to sinus rhythm . During conversion to sinus rhythm an AV junctional rhythm of short duration ( < 1 min ) was noticed in 5 patients and a short pause ( < 2 sec ) with or without an initial premature contraction in the remaining 21 . Disopyramide administration was not associated with side effects .  Diltiazem administration cause small ( < 20 mm Hg ) , transient ( < 30 min ) decrease of BP without symptoms with the exception of the patient with bradycardia in whom the BP decrease was significant ( 90/60 from 160/80 mm Hg ) followed by intense symptoms which lasted for six hours . CONCLUSIONS Diltiazem administration is extremely effective in conversion of paroxysmal atrial tachycardia to sinus rhythm . In addition it retards ventricular response in patients with atrial fibrillation and fluttering . Compared to disopyramide these effects of diltiazem are more pronounced and clinical ly pertinent A 24 h intravenous dosing regimen of amiodarone was design ed to reach a peak plasma concentration at 1 h and to maintain the concentration above a certain level during the infusion period . A r and omized , open-label , digoxin-controlled study was undertaken to observe the efficacy and safety of the dosing regimen of amiodarone in treating recent-onset , persistent , atrial fibrillation and flutter with ventricular rates above 130 beats.min-1 . Fifty patients with a mean age of 70 + /- 7 ( SD ) years were enrolled and r and omly assigned to receive either amiodarone intravenously ( n = 26 ) or digoxin ( n = 24 ) . Amiodarone HCl was infused over 24 h according to the following regimen : 5 mg.min-1 , 3 mg.min-1 , 1 mg.min-1 and 0.5 mg.min-1 for 1 , 3 , 6 and 14 h , respectively , for a 70-kg subject . Digoxin ( 0.013 mg.kg-1 ) was infused in three divided doses , each dose 2 h apart and infused over 30 min . The mean heart rates in the amiodarone group decreased significantly from 157 + /- 20 beats.min-1 to 122 + /- 25 beats.min-1 after 1 h ( P < 0.05 vs baseline ) , and then decreased further to stabilize at 96 + /- 25 beats.min-1 after 6 h ( P < 0.05 ) . The digoxin group had fewer dramatic alterations in heart rates , compared to the amiodarone group , in the first 8 h ( P < 0.05 , respectively ) . Maximum reduction was reached only after 8 h. The amiodarone infusion was prematurely aborted in two patients due to severe bradycardia and death after conversion in one patient and aggravation of heart failure in the other . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVE to determine whether digoxin is effective in converting atrial fibrillation of recent onset to normal sinus rhythm . DESIGN r and omized , double-blinded , placebo-controlled trial with a maximum 18-hour treatment period . SETTING emergency room and medical floors of a non-referral city hospital . PATIENTS consecutive sample of 36 patients with atrial fibrillation of 7 days ' duration or less , not on digitalis glycoside or anti-arrhythmic agents , with ventricular rate between 85 to 175 beats/min , without evidence of heart failure , acute myocardial infa rct ion , unstable angina , preexcitation syndrome , thyrotoxicosis , hypokalemia , renal impairment , or severe metabolic disturbances . INTERVENTIONS digoxin solution in capsules or identical placebo , given in doses of 0.6 , 0.4 , 0.2 , and 0.2 mg , at 0 , 4 , 8 , and 14 hours , respectively , or until conversion to sinus rhythm , whichever occurred first . Continuous electrocardiographic recording by Holter monitor .  MEASUREMENTS AND MAIN RESULTS nine of eighteen patients receiving digoxin  and 8 of 18 receiving  placebo  had a return to sinus rhythm within 18 hours of study entry ( 95 % confidence interval for the difference in proportions , -11 % to 22 % ) . Mean time to conversion was 5.1 hours in the digoxin group and 3.3 in the placebo group ( 95 % Cl , -3.6 to 7.0 hours ) . CONCLUSIONS spontaneous reversion to sinus rhythm is common in patients with atrial fibrillation of recent onset . Digitalization was not shown to affect the likelihood of reversion to sinus rhythm , and thus can not be recommended for this purpose in patients with atrial fibrillation BACKGROUND This study was design ed to assess the efficacy and safety of intravenous dofetilide in acute termination of atrial fibrillation ( AF ) and flutter ( AFL ) .  Dofetilide , an investigational class III antiarrhythmic agent , selectively inhibits the rapid component of the delayed rectifier potassium current , thus prolonging the effective refractory period and duration of the action potential . Dofetilide can be administered intravenously and has a rapid onset of electrophysiologic action . METHODS AND RESULTS Ninety-six patients with AF ( n = 79 ) or AFL ( n = 17 ) with a median arrhythmia duration of 62 days ( range 1 to 180 ) were r and omized to placebo ( n = 30 ) or 8 micrograms/kg IV dofetilide ( n = 66 ) over 30 minutes . Conversion was defined as termination of the atrial arrhythmia within 3 hours from the start of infusion . The conversion rate was 30.3 % after dofetilide and 3.3 % after placebo ( P < .006 ) . Conversion rate was higher in AFL than in AF : 64 % versus 24 % ( P = . 012 ) . In nonconverters , there was no statistically significant difference between the change in heart rate among the dofetilide-treated compared with the placebo-treated patients ( P = . 42 ) . Torsade de pointes ventricular tachycardia developed in 2 patients ( 3 % ) . In both patients , drug infusion was discontinued before the event because of prolongation of the QT interval . CONCLUSIONS Intravenous dofetilide is effective in acute termination of AF and AFL of medium duration , with a particularly high efficacy rate in AFL . A small but serious risk of proarrhythmia must be anticipated To compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation ( AF ) , 70 patients were entered into a r and omized , double-blind study . Of these , 35 received amiodarone and 35 sotalol . There were no significant differences in baseline clinical characteristics between groups . Patients with ejection fraction < 40 % or clinical ly significant heart disease were excluded . Patients r and omized to amiodarone began with 800 to 1,600 mg/day for 7 to 14 days orally . After the initial loading phase , the drug dose was tapered to maintenance levels over 7 to 12 days ; thereafter , therapy was generally maintained at a dosage of 200 mg/day . The sotalol dosage was 80 to 360 mg twice daily , as tolerated . Follow-up clinical evaluations were conducted at 1 , 2 , 4 , 6 , 9 , and 12 months . The proportion of patients remaining in sinus rhythm on each agent was calculated for the 2 groups using the Kaplan-Meier method . Ten of the 35 patients who were taking amiodarone developed AF during the 12-month observation period , compared with 21 of the 35 who were taking sotalol ( p = 0.008 ) . No significant effect of sex , age , left atrial size , or type of AF could be detected that increased the risk of development of AF . We conclude that both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with recurrent symptomatic AF but that amiodarone is the more effective of the 2 drugs for this purpose OBJECTIVES This study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation ( AF ) . BACKGROUND Biphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation , but data regarding biphasic shocks for conversion of AF are still emerging . METHODS In an international , multicenter , r and omized , double-blind clinical trial , we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF . Patients received up to five shocks , as necessary for conversion : 100 J , 150 J , 200 J , a fourth shock at maximum output for the initial waveform ( 200 J biphasic , 360 J monophasic ) and a final cross-over shock at maximum output of the alternate waveform . RESULTS Analysis included 107 monophasic and 96 biphasic patients . The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels ( 100 J : 60 % vs. 22 % , p < 0.0001 ; 150 J : 77 % vs. 44 % , p < 0.0001 ; 200 J : 90 % vs. 53 % , p < 0.0001 ) . Through four shocks , at a maximum of 200 J , biphasic performance was similar to monophasic performance at 360 J ( 91 % vs. 85 % , p = 0.29 ) . Biphasic patients required fewer shocks ( 1.7 + /- 1.0 vs. 2.8 + /- 1.2 , p < 0.0001 ) and lower total energy delivered ( 217 + /- 176 J vs. 548 + /- 331 J , p < 0.0001 ) . The biphasic shock waveform was also associated with a lower frequency of dermal injury ( 17 % vs. 41 % , p < 0.0001 ) . CONCLUSIONS For the cardioversion of AF , a biphasic shock waveform has greater efficacy , requires fewer shocks and lower delivered energy , and results in less dermal injury than a monophasic shock waveform Oral verapamil has previously been shown to reduce heart rate at rest and during mild exercise in chronic atrial fibrillation . Its efficacy in improving cardiovascular performance at higher levels of exercise and its safety were investigated in a prospect i ve , r and omized , placebo controlled double-blind study preceded by an open label titration phase in 20 digitalized patients with chronic atrial fibrillation .  Maximal exercise capacity was improved ( from 522 + /- 257 to 806 + /- 348 work units , p less than 0.0005 ) when tested by a st and ardized multistage ergometry exercise test .  Heart rate was also reduced at rest , at the end of 3 minutes of 300 KPM exercise , and at the point of maximal exercise . Blood pressure and double product were also reduced . Its efficacy and safety may make verapamil the treatment of choice in chronic atrial fibrillation Currently d , l-sotalol is widely used to prevent recurrence of atrial fibrillation and /or atrial flutter , although a r and omized dose-response study has not previously been conducted to guide therapy for this indication . This study summarizes findings of a double-blind , placebo-controlled , multicenter , r and omized trial evaluating the efficacy , safety , and dose-response relation of 3 fixed doses of d , l-sotalol ( 80 , 120 , and 160 mg twice daily ) for the maintenance of sinus rhythm in 253 patients with atrial fibrillation and /or atrial flutter . All patients were in sinus rhythm at r and omization . Treatment ( 69 patients on placebo , 59 on 80 mg , 63 on 120 mg , and 62 on 160 mg given twice daily ) was continued for 12 months or until documented recurrence of symptomatic atrial fibrillation and /or flutter . Transtelephonic electrocardiographic monitoring  was used to detect symptomatic recurrences . Demographic characteristics were not different in the 4 groups . Structural heart disease was present in 57 % of patients . Patients with a history of heart failure were excluded . The time from r and omization to symptomatic arrhythmia recurrence was significantly longer in the 2 higher d , l-sotalol dose groups than in the placebo group . The median times to recurrence were 27 , 106 , 229 , and 175 days for the placebo , 80 , 120 , and 160 mg groups , respectively . There were no deaths or cases of torsade de pointes , sustained ventricular tachycardia , or ventricular fibrillation reported . Thus , d , l-sotalol appeared to be both safe and effective in maintaining sinus rhythm in patients with symptomatic atrial fibrillation and /or flutter . Further , the 120-mg twice daily dose appeared to provide the most favorable benefit and /or risk STUDY OBJECTIVE To compare the effects of i.v . diltiazem and i.v . digoxin on ventricular rate control in the emergency treatment of acute atrial fibrillation and flutter ( AFF ) . METHODS This prospect i ve , r and omized , open-label trial involved 30 consecutive patients who presented with acute AFF to the emergency department of an urban , 420-bed community teaching hospital from April 1993 through March 1994 . Exclusion criteria included systolic blood pressure lower than 100 mm Hg , treatment with calcium-channel blockers other than diltiazem , lack of informed consent , and objection of the private physician . Patients were r and omly assigned to receive either i.v . diltiazem alone , i.v . digoxin alone , or both . Heart rate control was defined as a ventricular rate of less than 100 beats/minute . I.v . digoxin , 25 mg , was given as a bolus at time 0 and at time 30 minutes . An initial dose of .25 mg/kg diltiazem was given intravenously over the first 2 minutes , followed by a dose of .35 mg/kg at time 15 minutes and then a titratable i.v . infusion at a rate of 10 to 20 mg/hour to maintain heart rate control . The dosing regimens were the same whether the drugs were given alone or in combination . Heart rhythm , heart rate , and blood pressure were measured at time 0 , 5 , 10 , 15 , 30 , 60 , 120 , and 180 minutes . Statistical significance was assessed with the use of Student 's t test and ANOVA methodology . RESULTS At time 0 , the heart rate ( mean + /- SD ) was 150 + /- 19 beats/minute in the diltiazem group and 144 + /- 12 in the digoxin group ( difference not significant , P = .432 ) . The decrease in heart rate from time 0 reached statistical significance at time 5 minutes in the diltiazem group ( P = .0006 ) ; the mean rates at time 5 minutes were 111 + /- 26 beats/minute for diltiazem and 144 + /- 13 for digoxin . The decrease in heart rate achieved with digoxin did not reach statistical significance until time 180 minutes ( P = .0099 ) , at which time the rates were 90 + /- 13 for diltiazem and 117 + /- 22 for digoxin . CONCLUSION Treatment of acute AFF with i.v . diltiazem decreases ventricular heart rate significantly within 5 minutes , compared with 3 hours for treatment with i.v . digoxin . No advantage was noted within 3 hours for i.v . treatment with a combination of diltiazem and digoxin . I.v . diltiazem is superior to i.v . digoxin in the emergency control of ventricular rate in acute AFF and should be considered as a drug of choice for this condition . This study was not large enough to adequately assess adverse effects , and further studies may be warranted for clinical validation The results of the long-term follow-up of 119 patients who had DC cardioversion performed are described . All patients had had corrective cardiac surgery for chronic rheumatic valvar heart disease . The poor prognosis for maintenance of sinus rhythm in this type of patient is emphasized . Of the total patients , 83 per cent were converted to sinus rhythm , but relapses were common in those who had atrial fibrillation before operation . Only 40 per cent of such patients maintained sinus rhythm for 2 months , 15 per cent for 1 year , and 9 per cent for 2 years . By contrast , when atrial fibrillation occurred for the first time in the post-operative period , 82 per cent maintained sinus rhythm for 2 years after conversion . Post-operative DC cardioversion is in general not recommended for patients with rheumatic heart disease and atrial fibrillation unless atrial fibrillation occurs for the first time in the post-operative period . A controlled trial of prophylactic quinidine is reported and shows no significant increase in the number of patients remaining in sinus rhythm as compared with a control group not receiving quinidine In some patients with chronic atrial fibrillation , treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress . Findings of a few clinical studies suggest that beta blockade in combination with digitalis therapy may be of benefit in these patients . In a r and omized , double-blind , placebo-controlled , parallel-group , 8-week study of 32 patients with chronic atrial fibrillation , the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol .  Criteria for entry into the study included ventricular rate at rest greater than or equal to 80/min or greater than or equal to 120/min with exercise , and serum digoxin levels within the therapeutic range . After digoxin dose titration to produce therapeutic levels , digoxin dosage remained constant throughout the balance of the study . After a 2-week , single-blind placebo lead-in period , patients were r and omized to receive either digoxin plus placebo or a combination of digoxin and nadolol . The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated . Twenty-four hour ambulatory electrocardiographic ( Holter ) recordings , symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods . Comparing endpoint with baseline , results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant ( p less than 0.001 ) decreases in 24 hour average ( 78 + /- 4 to 63 + /- 3 ) . ( ABSTRACT TRUNCATED AT 250 WORDS 1 . The ideal drug treatment for atrial fibrillation will control resting heart rate , blunt exercise induced tachycardia whilst not exacerbating nocturnal bradycardia . Monotherapy with digoxin may not be ideal . We have compared the effect of combining digoxin ( 0.25 mg daily ) with atenolol 50 mg and 100 mg or pindolol 5 mg twice daily and 15 mg twice daily in a cross-over r and omised single-blind trial in eight symptomatic patients ( six male ; mean age 62 years ) with poorly controlled atrial fibrillation . 2 . Heart rate control was measured by  24 h ECG at baseline on digoxin therapy and after 2 weeks with each treatment . Symptom scores for breathlessness and palpitation were measured using visual analogue scales . 3 . The addition of both beta-adrenoceptor blockers significantly reduced mean diurnal maximum heart rate from baseline ( all P < 0.001 ANOVA ) . Atenolol at both doses caused a greater reduction than either dose of pindolol ( P < 0.001 ANOVA ) . Nocturnal maximum heart rate was not significantly reduced from baseline by either beta-adrenoceptor blocker , but both doses of pindolol caused increases in nocturnal maximum heart rate compared with atenolol ( P < 0.001 ANOVA ) . 4 . Atenolol caused a reduction in diurnal minimum heart rate compared with baseline and caused a reduction in nocturnal minimum heart rate whereas pindolol caused an increase ( P < 0.001 ANOVA ) . 5 . Atenolol 100 mg caused longer nocturnal pauses compared with baseline but pindolol 15 mg twice daily reduced the number of nocturnal pauses > 1.5 s ( P = 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Nine male patients ( mean age 65 yr ) with chronic atrial fibrillation underwent maximal exercise testing  during placebo , beta-adrenergic ( celiprolol , 600 mg ) , or calcium ( diltiazem , 30 or 60 mg four times daily ) channel blockade . The results were analyzed to determine which factors most closely related to ratings of perceived exertion ( RPE ) during exercise . Heart rate ( HR ) , blood pressure ( BP ) , oxygen uptake ( VO2 ) , minute ventilation ( VE ) , and carbon dioxide production ( VCO2 ) were evaluated at rest , 3.0 mph/0 % grade , the gas exchange anaerobic threshold ( ATge ) , 80 % of placebo maximal O2 uptake , and maximal exercise . Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo ; these effects were more profound during beta-adrenergic blockade and as exercise progressed . Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR , VO2 , VE , and VCO2 during the three treatments ( r = 0.76 to 0.92 , P less than 0.001 ) . Although RPE was significantly correlated with HR during placebo and diltiazem therapy ( r = 0.45 , P less than 0.01 ) , this was not the case during beta-adrenergic blockade ( r = 0.31 , NS ) . Slope of the regression lines between RPE and VO2 , VE , and VCO2 did not differ between the three treatments . Slope of the regression lines between RPE and HR differed only during calcium channel blockade . Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE , VO2 , and HR , these results suggest that VE is more closely related to RPE than the other parameters Sotalol is an antiarrhythmic agent with combined beta-blocking and class III antiarrhythmic properties . This study was design ed to assess the safety and efficacy of sotalol in terminating supraventricular tachycardia ( SVT ) , atrial fibrillation ( AFib ) , and atrial flutter ( AFl ) .  Ninety-three patients with spontaneous or induced SVT ( n = 45 ) or AF ( AFib or AFl ; n = 48 ) with a ventricular rate of > or = 120 beats/min were studied . In the first phase , the double-blind phase , patients were r and omly assigned to receive placebo or intravenous ( i.v . ) sotalol , 1.0 or 1.5 mg/kg . If SVT or AF did not convert to sinus rhythm or if the ventricular rate did not slow to < 100 beats/min within 30 minutes , patients then entered the second phase , the open-label phase , which also lasted 30 minutes , and were given 1.5 mg/kg iv sotalol . In the SVT group , during the double-blind phase conversion to sinus rhythm occurred in 2 ( 14 % ) of 14 of patients who received placebo , 10 ( 67 % ) of 15 who received sotalol , 1.0 mg/kg ( p < 0.05 vs placebo ) , and 10 ( 67 % ) of 15 who received 1.5 mg/kg sotalol ( p < 0.05 vs placebo ) ; during the open-label phase , 1.5 mg/kg i.v . sotalol converted 7 ( 41 % ) of 17 of patients . In the AF group , during the double-blind phase conversion to sinus rhythm occurred in 2 ( 14 % ) of 14 of patients who received placebo , 2 ( 11 % ) of 18 who received 1.0 mg/kg sotalol ( p not significant [ NS ] vs placebo ) , and 2 ( 13 % ) of 16 who received 1.5 mg/kg sotalol ( p = NS vs placebo ) ; in these groups , a > 20 % reduction of ventricular rate without conversion to sinus rhythm occurred in 0 ( 0 % ) of 14 , 13 ( 72 % ) of 18 ( p < 0.05 vs placebo ) , and 12 ( 75 % ) of 16 of patients ( p < 0.05 vs placebo ) , respectively ; during the open-label phase , 1.5 mg/kg i.v . sotalol converted 7 ( 30 % ) of 23 of patients . The most common adverse events were hypotension and dyspnea . During the double-blind phase they occurred in 10 % of patients who received placebo , 9 % of those who received 1.0 mg/kg i.v . sotalol ( p = NS vs placebo ) , and 10 % of those who received 1.5 mg/kg i.v . sotalol ( p = NS vs placebo ) . Most of these events were mild to moderate , but all were transient and clinical ly manageable . ( ABSTRACT TRUNCATED AT 400 WORDS UNLABELLED Eighty-seven patients with recent onset atrial fibrillation ( < or = 8 days ) without clinical signs of heart failure were r and omly allocated to one of the following treatments : ( i ) oral propafenone ( 600 mg as a loading dose followed after 8 h by 300 mg t.i.d . ) ; ( ii ) intravenous digoxin as acute scheme ( up to 1.125 mg/24 h ) followed after 6 h by hydroquinidine chlorhydrate ( total dose , 1350 mg ) ; or ( iii ) placebo . The patients were su bmi tted to Holter monitoring for 48 h. RESULTS propafenone achieved higher successful conversion rates at 6 , 12 and 24 h compared either with placebo ( 62 % vs. 17 % , 83 % vs. 34 % ; 86 % vs. 55 % ; P < 0.01 , respectively ) or with digoxin at 6 h ( 62 % vs. 38 % ; P < 0.05 ) and digoxin plus quinidine at 12 h ( 83 % vs. 48 % ; P < 0.05 ) . At 48 h , a placebo  conversion rate of 76 % was observed with consequent lack of any significant difference with the active treatments . Mean conversion times within 48 h were 267 + /- 238 min for propafenone , 648 + /- 631 min for digoxin plus quinidine ( P < 0.01 vs. propafenone ) and 893 + /- 622 min for placebo ( P < 0.001 vs. propafenone ) .  Propafenone and digoxin plasma levels were within the therapeutic range . Asymptomatic phases of atrial flutter with > or = 2:1 atrio-ventricular conduction ratio were observed during Holter monitoring , before conversion to sinus rhythm , in four patients treated with propafenone , in one patient taking digoxin plus quinidine and in four patients with placebo . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Spontaneous conversion of recent onset paroxysmal atrial fibrillation  to  normal sinus rhythm  occurs commonly and is not affected by low-dose amiodarone treatment . METHODS In a r and omized , placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset ( < 48 h ) we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour ( total 3 g ) and intravenous placebo .  Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy . RESULTS Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients ( 64 % ) in the placebo group , most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension , ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm , ejection fraction below 45 % or significant mitral regurgitation . However , in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present . In such patients the spontaneous conversion rate was approximately 90 % . The conversion rate during 24 h of treatment in the amiodarone group was 92 % ( P=0.0017 , compared to the placebo group ) . In this group , the conversion rate was largely unaffected by baseline characteristics . Of the 18 patients who did not convert with placebo , 15 ( 85 % ) converted after being crossed over to amiodarone . All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month . In patients still in atrial fibrillation after 8 h of treatment , the pulse rate decreased significantly more in the amiodarone as compared to the placebo group ( 83+/-15 vs 114+/-20 beats . min(-1 ) , P=0.0014 ) . CONCLUSION The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90 % in specific clinical and echocardiographically defined subgroups . Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation . However , such treatment should be reserved for patients with unfavourable risk factor profiles , not converting during 8 h of observation or requiring rate control To compare the efficacy and safety of sotalol and quinidine  after conversion of atrial fibrillation ( AF ) of < 6 months , a prospect i ve multicenter trial enrolled 121 patients who were r and omized to receive dl-sotalol ( 160 to 320 mg/day , 58 patients ) or quinidine sulfate ( 600 to 800 mg/day , 63 patients ) . Patients with left ventricular ejection fraction of < 0.40 or left atrial diameter > 5.2 cm were excluded . After 6 months of follow-up , using the Kaplan-Meier method , the probabilities of success were comparable between sotalol ( 74 % ) and quinidine ( 68 % ) , but recurrences occurred later with sotalol than with quinidine ( 69 vs 10 days , p < 0.05 ) . Four patients developed proarrhythmic events , 3 ( 5 % ) with sotalol and 1 ( 2 % ) with quinidine , which were all associated with diuretic therapy . In patients converted from recent-onset AF ( < or = 72 hours ) , sotalol was more effective than quinidine ( 93 % vs 64 % , p = 0.01 ) , whereas in chronic AF ( > 72 hours ) , quinidine was more effective than sotalol ( 68 % vs 33 % , p < 0.05 ) . During recurrences , the ventricular rate was significantly reduced in patients taking sotalol ( 98 to 82 beats/min , p < 0.05 ) . Independent predictors of therapeutic success were recent-onset AF in the sotalol group ( p < 0.001 ) and absence of hypertension in the quinidine group ( p < 0.05 ) . In conclusion , sotalol and quinidine have comparable efficacy and safety for the maintenance of sinus rhythm in the overall group . In recent-onset AF , sotalol was more effective , whereas in chronic AF , quinidine had a better result . Recurrences occurred later with sotalol when compared with quinidine . Because of proarrhythmia , these drugs should be used judiciously in patients on diuretic therapy In patients with chronic nonrheumatic atrial fibrillation , prophylaxis of peripheral arterial embolism is strongly indicated . LMWHs may be an alternative regimen if contraindications for oral anticoagulants are present . In the present study the effect of LMWH on the incidence of embolism in atrial fibrillation has been studied in 75 consecutive patients in comparison to no specific treatment . Patients received one daily injection of the LMWH CY 216 ( n = 35 ) subcutaneously over a period of 6 months . Patients of the control group ( n = 40 ) were observed over the same period of time . In the group treated with CY 216 , three embolic events ( 8.6 % ) occurred , of which two were localized in the cerebrum . One of these two cerebral embolic events was fatal . In the control group , eight embolic events ( 20 % ) occurred , six of these were intracerebral and , of these , five were fatal . An even more pronounced difference between the groups was observed on evaluation of the patients with preceding cerebral embolism . Of 15 patients treated with LMWH  , one extracerebral nonfatal embolism occurred . In the control group three of the seven patients ( 43 % ) experienced fatal reembolism . The results show that in patients with atrial fibrillation one daily subcutaneous injection of LMWH reduces the incidence of arterial embolism to about one third . No adverse effects were observed during the 6-month treatment period with LMWH OBJECTIVE The main aim of the study was to evaluate the safety and efficacy of propafenone versus quinidine as an initial choice in treatment of symptomatic paroxysmal atrial fibrillation .  DESIGN The study consisted of a 3-month treatment with oral propafenone hydrochloride or quinidine sulphate in patients with paroxysmal symptomatic atrial fibrillation , according to a double-blind r and omized system . SETTING The study was performed in the out-patient clinic of university hospital . MAIN OUTCOME MEASURES The effects of the two drugs on attack frequency , ventricular rate and symptoms of symptomatic paroxysmal atrial fibrillation . RESULTS In the oral propafenone group ( n = 48 ) , two patients ( 4 % ) discontinued the treatment because of dizziness . In the 46 patients who continued the treatment , the attack frequency decreased from 11 + /- 3 times per week at baseline to 1 + /- 1 times per week after treatment ( P < 0.01 ) . Forty ( 87 % ) out of the 46 patients had effective response to oral propafenone ( more than 75 % reduction of symptomatic arrhythmic attacks ) on a mean dose of 615 + /- 10 mg day-1 ; the decrease in attack frequency was from 10 + /- 3 to 1 + /- 1 times per week . Twenty-three ( 50 % ) patients were free from recurrence of symptomatic paroxysmal atrial fibrillation . Comparisons of symptom scores for patients ( n = 23 ) with attacks of paroxysmal atrial fibrillation after oral propafenone treatment showed that there was a significantly lower symptom score of palpitation , asthenia , effort dyspnea , dizziness , rest dyspnea and chest oppression in attacks of paroxysmal atrial fibrillation after propafenone treatment ( 11.05 + /- 3.78 versus 7.60 + /- 3.46 , P < 0.01 ) . From the oral quinidine group ( n = 48 ) , two patients ( 4 % ) discontinued treatment because of gastrointestinal discomfort . In the 46 patients who continued the treatment , the attack frequency decreased from 11 + /- 4 times per week at baseline to 3 + /- 2 times per week after treatment ( P < 0.01 ) . Twenty-one ( 46 % ) out of the 46 patients had effective response to oral quinidine on a mean dose of 1067 + /- 462 mg day-1 , with a decrease in attack frequency from 12 + /- 3 to 1 + /- 1 times per week . Only 10 ( 22 % ) patients were free from recurrence of paroxysmal atrial fibrillation . Comparisons of symptom scores for patients ( n = 36 ) with attacks of paroxysmal atrial fibrillation after quinidine treatment showed that there was no significant decrease of symptom score in attacks of atrial fibrillation ( 10.65 + /- 3.92 versus 10.20 + /- 3.80 , P = 0.57 ) . Furthermore , the percentage decrease of ventricular rate during atrial fibrillation was significantly greater in patients with propafenone ( -25 + /- 4 % versus -8 + /- 3 % , P < 0.01 ) . CONCLUSIONS Oral propafenone appeared to be more effective than quinidine in suppressing attacks and alleviating symptoms of paroxysmal atrial fibrillation Abstract Amiodarone and verapamil are well-known antiarrhythmic drugs used for treatment of ventricular and supraventricular arrhythmias . Although verapamil is the drug of choice for control of the atrioventricular node , it has also been reported to terminate atrial fibrillation . 1–3 Amiodarone has been used extensively for drug-refractory ventricular tachycardia but seldom for termination of paroxysmal atrial fibrillation . 4–6 To our knowledge , no comparative study with amiodarone and verapamil has been reported . Because of this , we compared the efficacy of intravenous amiodarone versus verapamil for conversion of paroxysmal atrial fibrillation to sinus rhythm in a single-blind r and omized study STUDY OBJECTIVE A prospect i ve , r and omized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone ( active treatment ) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours . METHODS We prospect ively r and omly assigned 120 patients with atrial fibrillation of less than 24 hours ' duration to treatment with sotalol , amiodarone , or digoxin using a single intravenous dose followed by 48 hours of oral treatment . Patients had ECG monitoring for 48 hours , and time of reversion , adequacy of rate control , and numbers of adverse events were compared . After 48 hours , those still in atrial fibrillation underwent cardioversion according to a st and ardized protocol . After 48 hours of therapy and attempted cardioversion , the number of patients whose rhythms had successfully reverted were compared . RESULTS There was a significant reduction in the time to reversion with both sotalol ( 13 . 0+/-2.5 hours , P < .01 ) and amiodarone ( 18.1+/-2.9 hours , P < .05 ) treatment compared with digoxin only ( 26.9+/-3.4 hours ) . By 48 hours , the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group ( 95 % versus 78 % , P < .05 ; risk ratio 5.4 , 95 % confidence interval [ CI ] 1.5 to 19.2 ) . In those patients whose rhythms did not revert to sinus rhythm , there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin . There were also fewer adverse events in the active treatment group compared with the rate control group . CONCLUSION Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs ( sotalol or amiodarone ) improves complication-free 48-hour reversion rates compared with rate control with digoxin OBJECTIVES Currently available antiarrhythmic drugs have limited efficacy for short-term , rapid termination of atrial fibrillation and atrial flutter . BACKGROUND Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current . It can be administered intravenously and has a rapid onset of electrophysiologic effects . METHODS The efficacy and safety of ibutilide were studied in 200 patients with atrial flutter > 3 h in duration or atrial fibrillation 3 h to 90 days in duration . Patients were r and omized to receive a single intravenous dose of placebo or an infusion of ibutilide fumarate at 0.005 , 0.010 , 0.015 or 0.025 mg/kg body weight over 10 min . Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion . Forty-one patients received placebo  and 159 received ibutilide ( 0.005 mg/kg [ n = 41 ] , 0.010 mg/kg [ n = 40 ] , 0.015 mg/kg [ n = 38 ] or 0.025 mg/kg [ n = 40 ] ) . RESULTS The arrhythmia terminated in 34 % of drug-treated patients . The rates of successful arrhythmia termination were 3 % for placebo and 12 % , 33 % , 45 % and 46 % , respectively , for 0.005- , 0.010- , 0.015- and 0.025-mg/kg ibutilide . The placebo and 0.005-mg/kg ibutilide groups had lower success rates than all other dose groups ( p < 0.05 ) . The mean time to termination of the arrhythmia was 19 min ( range 3 to 70 ) from the start of infusion . Successful arrhythmia termination was not affected by enlarged left atrial diameter , decreased ejection fraction , presence of valvular heart disease or the use of concomitant medications ( beta-adrenergic blocking agents , calcium channel blocking agents or digoxin ) . Arrhythmia termination was not predicted by the magnitude of corrected QT interval prolongation but was associated with a shorter duration of atrial arrhythmia . The most frequent adverse events in ibutilide-treated patients were sustained and nonsustained polymorphic ventricular tachycardia ( 3.6 % ) . All patients with sustained polymorphic ventricular tachycardia were successfully treated with direct current cardioversion and had no recurrence . The occurrence of proarrhythmia did not correlate with ibutilide plasma concentration . CONCLUSIONS These data demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter OBJECTIVE To analyze the efficacy of an IV combination of diltiazem and digoxin vs IV diltiazem alone for acute ventricular rate control in patients with atrial fibrillation . DESIGN Prospect i ve , r and omized , open-label study . PATIENTS AND METHODS Fifty-two patients with atrial fibrillation and uncontrolled ventricular rates were r and omized to receive either an IV combination of diltiazem and digoxin or IV diltiazem alone and were observed for 12 h. The successful rate control was defined as a ventricular rate < 100 beats per minute ( bpm ) persisting for 1 h or conversion to sinus rhythm . The loss of rate control was defined as an increase in the ventricular rate to > 100 bpm persistently for > 30 min or rebound to atrial fibrillation . RESULTS In both treatment arms ( n = 26 each ) , all patients achieved successful and comparable ventricular rate control at 12 h. The mean ( + /- SD ) time taken to achieve successful rate control was shorter in the combination arm ( 15 + /- 16 vs. 22 + /- 22 min ) . Six patients in the combination arm and 11 in the diltiazem-alone arm experienced episodes of loss of rate control . This loss in the combination arm was less than that in the diltiazem-alone arm ( 14 vs 39 episodes ; p = 0.05 ) . The loss of rate control per patient in the combination arm was also less than that in the diltiazem-alone arm ( 2.0 + /- 1.0 vs. 3.5 + /- 1.9 episodes per patient ; p = 0.04 ) . CONCLUSIONS This study demonstrates that in patients with atrial fibrillation who have a rapid ventricular response , the IV combination of diltiazem and digoxin results in a more efficacious ventricular rate control with fewer fluctuations than that achieved by therapy with IV diltiazem alone Atrial fibrillation ( AF ) is one of the most frequent dysrhythmias in patients coming to emergency departments ( EDs ) , and pharmacological treatment is frequently performed . The aim of this r and omized placebo-controlled multicenter trial was to compare propafenone ( a class 1C antidysrhythmic agent ) , administered i.v . in the ED , with placebo in the treatment of recent-onset AF ( < 72 h ) . We r and omly allocated 156 patients ( 88 males ; 68 females ) from 18 to 80 years old , with recent-onset AF , to receive i.v . propafenone ( 2 mg/kg for 10 min ) or the matching placebo . The patients were followed for 2 h. Exclusion criteria were the presence of one of the following : lack of informed consent , clinical evidence of heart failure , clinical hyperthyroidism , recent acute myocardial infa rct ion , atrioventricular block , cardiac valve dysfunction , a history of bronchial asthma , and current treatment with antidysrhythmic agents including digitalis . The two groups did not differ significantly in terms of sex , age , body weight , or estimated time elapsed since the beginning of atrial fibrillation . Conversion to sinus rhythm occurred in 13 of the 75 patients who received the placebo ( 17.3 % ) and in 57 of the 81 patients who were given propafenone ( 70.3 % ) . In conclusion , intravenous propafenone administration in the ED can be considered a safe and effective approach for converting AF to sinus rhythm OBJECTIVES We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate ( VR ) in patients with chronic atrial fibrillation ( CAF ) . BACKGROUND Systematic comparison of st and ardized drug regimens on 24 h VR control in CAF have not been reported . METHODS In 12 patients ( 11 male , 69+/-6 yr ) with CAF , the effects on VR by 5 st and ardized daily regimens : 1 ) 0.25 mg digoxin , 2 ) 240 mg diltiazem-CD , 3 ) 50 mg atenolol , 4 ) 0.25 mg digoxin + 240 mg diltiazem-CD , and 5 ) 0.25 mg digoxin + 50 mg atenolol ; were studied after 2 week treatment assigned in r and om order . The VR data were analyzed by ANOVA with repeated measures . The circadian phase differences were evaluated by cosinor analysis . RESULTS The 24-h mean ( + /-SD ) values of VR ( bpm ) were - digoxin : 78.9 + /- 16.3 , diltiazem : 80.0+/-15.5 , atenolol : 75.9+/-11.7 , digoxin + diltiazem : 67.3+/-14.1 and digoxin + atenolol : 65.0+/-9.4 . Circadian patterns were significant in each treatment group ( p < 0.001 ) . The VR on  digoxin + atenolol  was significantly lower than that on digoxin ( p < 0.0001 ) , diltiazem ( p < 0.0002 ) and atenolol ( p < 0.001 ) . The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol ( p < 0.03 ) . During exercise , digoxin and digoxin + atenolol treatments result ed in the highest and lowest mean VR respectively . The exercise Time-VR plots of all groups were nearly parallel ( p = ns ) . The exercise duration was similar in all treatment groups ( p = ns ) . CONCLUSIONS This study indicates that digoxin and diltiazem , as single agents at the doses tested , are least effective for controlling ventricular rate in atrial fibrillation during daily activity . Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node . The data provides a basis for testing the effects of  chronic suppression of diurnal fluctuations of VR  on left atrial and ventricular function in CAF Background : Pharmacological conversion of paroxysmal atrial fibrillation is frequently necessary . The aim of this study was to compare intravenous propafenone , a class Ic antiar‐rhythmic agent , with placebo in paroxysmal atrial fibrillation ( AF ) of recent onset ( < 72 h ) AIMS To evaluate the efficacy and safety of a single loading oral dose of propafenone in the interruption of recent-onset atrial fibrillation . METHODS After a complete medical history , physical examination , 12-lead ECG , chest X-ray , and routine biochemical laboratory testing , 55 consecutive patients with recent-onset atrial fibrillation were r and omized double-blind in the emergency department for the administration of either a single oral dose ( 450 to 750 mg ) of propafenone ( 29 cases ) or a placebo ( 26 cases ) . After the 24-h observation period , comprehensive echocardiographic examination was performed . RESULTS The groups were homogeneous as regards biological , clinical and echocardiographic characteristics . Two hours after treatment , 12 patients ( 41 % ) on propafenone but only two ( 8 % ) on placebo had converted to sinus rhythm ( P = 0.005 ) . This striking difference was maintained 6 h after treatment ( 65 vs 31 % ; P = 0.015 ) but lessened at 12 h ( 69 % vs 42 % ; P = 0.060 ) and was insignificant at the end of the 24-h treatment period ( 79 % , vs 73 % ; P = 0.752 ) . Apart from hypotension , transient in three cases and sustained in one whose later echocardiographic examination demonstrated left systolic ventricular dysfunction , propafenone was well tolerated . CONCLUSION Although there is no significant difference in the rates of conversion 24 h after treatment , propafenone works faster than placebo in achieving sinus rhythm . This rapid action of oral propafenone can be useful to solve quickly the clinical problems of a high proportion of patients arriving at the emergency department with acute atrial fibrillation Atrial  fibrillation ( AF ) is a common arrhythmia in elderly persons and a common cause of embolic stroke . Most studies of the prevalence and correlates of AF have used selected , hospital-based population s. The Cardiovascular Health Study is a population -based , longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years .  AF  was diagnosed in 4.8 % of women and in 6.2 % of men at the baseline examination , and prevalence was strongly associated with advanced age in women . Prevalence of AF  was 9.1 % in men and women with clinical cardiovascular disease , 4.6 % in patients with evidence of sub clinical but no clinical cardiovascular disease , and only 1.6 % in subjects with neither clinical nor sub clinical cardiovascular disease . A history of congestive heart failure , valvular heart disease and stroke , echocardiographic evidence of enlarged left atrial dimension , abnormal mitral or aortic valve function , treated systemic hypertension , and advanced age were independently associated with the prevalence of AF .  The low prevalence of AF in the absence of clinical and sub clinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called " lone atrial fibrillation " in the elderly This study was conducted to evaluate the clinical efficacy of intravenous ( i.v . ) magnesium sulphate 2 gm bolus in sustained supraventricular tachycardia ( SVT ) and atrial flutter-fibrillation with fast ventricular rate of more than 160/min ( AF-FVR ) and to compare it with i.v . verapamil 5 mg . In this r and omised controlled trial , 68 cases of SVT and 86 cases of AF-FVR were studied . Patients with evidence of renal dysfunction and systolic blood pressure less then 90 mm Hg were excluded . Response was considered when the heart rate fell to less than 100/min . In SVT , 33.3 % ( 11 out of 33 ) responded to magnesium sulphate which was significantly less than verapamil ( 23 out of 35 , 65.7 % ) p = 0.007 . Similarly , in AF-FVR , response was more with verapamil ( 25 out of 45 , 55.6 % ) than magnesium sulphate ( 8 out of 41 , 19.5 % ) p < 0.0001 . Response to magnesium sulphate was better in patients with IHD . There were no significant side effects , except flushing and sense of warmth with i.v . magnesium sulphate .  Serum magnesium rose significantly after i.v . magnesium bolus . Though magnesium sulphate is a weaker antiarrhythmic drug than verapamil , further studies are needed to identify subgroups of supraventricular tachyarrhythmias which would respond to magnesium sulphate STUDY OBJECTIVE To compare placebo vs two different regimens of propafenone administration -- intravenous administration or short-term oral loading -- in converting recent-onset atrial fibrillation to sinus rhythm . DESIGN Single-blind placebo-controlled study . PATIENTS Eighty-seven patients with atrial fibrillation of recent onset ( < or = 7 days ' duration ) admitted to the hospital without signs of organic heart disease ( n = 42 ) or with systemic hypertension without signs or symptoms of heart failure ( n = 45 ) . The patients were assigned r and omly to treatment with intravenous propafenone ( 29 patients ) , oral propafenone ( 29 patients ) , or placebo ( 29 patients ) . INTERVENTIONS Administration of propafenone intravenously ( 2-mg/kg bolus followed by 0.0078 mg/kg/min ) or as short-term oral loading ( 600 mg orally single dose ) . Patients were su bmi tted to Holter monitoring and conversion to sinus rhythm was evaluated at 1 , 3 , and 8 h. RESULTS Conversion to sinus rhythm was obtained within 1 h in 28 % with intravenous propafenone , in 3 % with oral propafenone , and in 3 % with placebo . At 3 h , the efficacy of intravenous propafenone ( 41 % ) and of oral propafenone ( 55 % ) were statistically superior to placebo ( 10 % of conversions ) and at 8 h either intravenous or oral propafenone were effective in almost two thirds of the patients with a statistical difference vs placebo , whose efficacy was 24 % . No major side effects were observed . CONCLUSIONS Propafenone as an oral loading dose is an efficacious and fast way of treating atrial fibrillation of recent onset and due to its simplicity of administration and safety can be preferred to the intravenous route AIMS A r and omized , double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation ( not due to haemodynamic alternations ) to sinus rhythm , and for rate control in converters and non-converters was set up . Outcome measures were conversion within 12 h ; time to conversion ; early rate control ; and stable slowing within 12 h. METHODS We studied 40 patients with recent onset ( < 1 week ) atrial fibrillation ; controls received saline intravenously , the other patients digoxin 1.25 mg .  RESULTS One patient converted before digoxin administration . Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo ( ns ) . The mean time to conversion tended to be shorter only for digoxin . Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters ( P < 0.05 ) . For all patients on digoxin , heart rate after 30 min was lower compared to baseline ( P < 0.002 ) and to placebo ( P < 0.02 ) . Persistent , stable slowing occurred only in 3/10 non-converters on digoxin ( P < 0.05 ) , and two patients developed bradyarrhythmias . QTc was shortened immediately after conversion in all patients . Converters had baseline characteristics similar to those of non-converters . CONCLUSIONS Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion , and provides weak rate control Thirty-nine patients with paroxysmal atrial fibrillation or supraventricular tachycardia r and omly received amiodarone or propafenone intravenously at home . Fifteen patients received amiodarone and 24 received propafenone ; 87.5 % of the patients who received propafenone and 40 % of the patients who received amiodarone were converted at home to sinus rhythm ( P less than .005 ) . The median time of conversion was 10 minutes ( range 5 to 35 ) for propafenone and 60 minutes ( range 20 to 130 ) for amiodarone ( P less than 0.005 ) . When either drug failed to terminate atrial tachydysrhythmias at home , the same drug always restored sinus rhythm with subsequent oral treatment during hospitalization . No major side effects were observed after the infusion of either drug . The incidence of minor side effects was not significantly different between the two drugs . Both the drugs are efficacious and safe in the acute management of primary supraventricular tachydysrhythmias .  Propafenone showed a greater rapidity of action The Canadian Atrial Fibrillation Anticoagulation Study was a r and omized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage . As a result of the publication of two other " positive " studies of similar design and objective , this study was stopped early before completion of its planned recruitment of 630 patients . There were 187 patients r and omized to warfarin and 191 to placebo .  Permanent discontinuation of study medication occurred in 26 % of warfarin-treated and 23 % of placebo-treated patients . The target range of the international normalized ratio was 2 to 3 . For the warfarin-treated patients , the international normalized ratio was in the target range 43.7 % of the study days , above it 16.6 % of the study days and below it 39.6 % of the study days . Fatal or major bleeding occurred at annual rates of 2.5 % in warfarin-treated and 0.5 % in placebo-treated patients . Minor bleeding occurred in 16 % of patients receiving warfarin and 9 % receiving placebo . The primary outcome event cluster was nonlacunar stroke , non central nervous systemic embolism and fatal or intracranial hemorrhage . Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication . The annual rates of the primary outcome event cluster were 3.5 % in warfarin-treated and 5.2 % in placebo-treated patients , with a relative risk reduction of 37 % ( 95 % confidence limits , -63.5 % , 75.5 % , p = 0.17 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation , because the prevention of recurrences can improve cardiac function and relieve symptoms . Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence , but this agent has not been tested in a large , r and omized trial . METHODS We undertook a prospect i ve , multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone . We r and omly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone , given in an open-label fashion . The patients in the group assigned to sotalol or propafenone underwent a second r and omization to determine whether they would receive sotalol or propafenone first ; if the first drug was unsuccessful the second agent was prescribed . Loading doses of the drugs were administered and electrical cardioversion was performed ( if necessary ) within 21 days after r and omization for all patients in both groups . The follow-up period began 21 days after r and omization . The primary end point was the length of time to a first recurrence of atrial fibrillation . RESULTS Of the 403 patients in the study , 201 were assigned to  amiodarone  and 202 to either sotalol ( 101 patients ) or propafenone ( 101 patients ) . After a mean of 16 months of follow-up , 71 of the patients who were assigned to amiodarone ( 35 percent ) and 127 of those who were assigned to sotalol or propafenone ( 63 percent ) had a recurrence of atrial fibrillation ( P<0.001 ) . Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone , as compared with 11 percent of those treated with sotalol or propafenone ( P=0.06 ) . CONCLUSIONS Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation Transesophageal echocardiography visualizes the left atrium and its appendage and is more sensitive than transthoracic echocardiography for diagnosing thrombi of the left atrium and the left atrial appendage and spontaneous echocardiographic contrast of the left atrium [ 1 - 3 ] . The left atrium and especially the left atrial appendage are the presumed sites of thrombus formation and sources of arterial emboli in patients with atrial fibrillation [ 4 ] . Patients with atrial fibrillation and a history of stroke or embolism were shown to have a higher prevalence of thrombi of the left atrium or the left atrial appendage , a higher prevalence of spontaneous echocardiographic contrast , and a larger left atrial appendage than patients with no history of stroke or embolism [ 2 , 5 , 6 ] . However , whether these abnormalities are predictors for stroke or embolism remains controversial [ 7 , 8 ] . Furthermore , no studies have determined whether transesophageal echocardiography helps to assess risk for stroke or embolism in out patients with atrial fibrillation who have no history of stroke or embolism or whether transesophageal echocardiography is useful in the decision to initiate anticoagulation . We therefore performed a prospect i ve , multicenter study of out patients with atrial fibrillation who had not recently had stroke . We sought to determine whether thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and size of the left atrial appendage are associated with stroke or embolism . Our hypothesis was that patients with thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and enlargement of the left atrial appendage have a higher rate of stroke or embolism than do patients without these abnormalities . The baseline clinical and echocardiographic characteristics of our study sample have been reported elsewhere [ 9 ] . Methods Patient Recruitment Our study was conducted in Austria and Slovakia . At the beginning of the study , general practitioners and internists from surrounding participating centers were informed about the study and were asked to refer patients who had constant or intermittent atrial fibrillation . At each patient 's first visit , a cardiologist recorded baseline data , associated illnesses , clinical characteristics ( definitions of which are listed in Appendix 2 ) , and the cause of atrial fibrillation . A 12-lead electrocardiogram was recorded on 2 separate days . We excluded patients with prosthetic valves and those who were already receiving anticoagulation . Current therapy with aspirin was not an exclusion criterion . Patients who had mitral valve stenosis or had recently had stroke were excluded because anticoagulation was indicated for such conditions . For the definition of recent stroke , we chose a cutoff value of 1 year because a previous study reported that the risk for recurrent stroke was increased in patients who had had an ischemic event in the previous year [ 10 ] . Echocardiography For transthoracic echocardiography , 2.5- or 3.5-MHz probes were used . For M-mode measurements , we applied the recommendations of the American Society of Echocardiography [ 11 ] . M-mode measurements were performed on-line and were documented on printouts . Regional wall-motion and valvular abnormalities were recorded . In patients without regional wall-motion abnormalities , left ventricular systolic function was assessed by calculation of left ventricular fractional shortening . For transesophageal echocardiography , biplane 5-MHz probes were used in 64 % of the patients and monoplane 5-MHz probes were used in 36 % . After local anesthesia with lidocaine spray was administered , the probe was introduced into the nonse date d patients , who lay on their left side . The entire study was recorded on S-VHS videotapes . The cardiac chambers and valves were investigated by using all obtainable views [ 12 , 13 ] . Special care was taken to visualize the whole cavity of the left atrium and its appendage from different planes , with the tip of the probe slightly flexed . The size of the left atrial appendage was measured off-line . A frame that best visualized the left atrial appendage with respect to its orifice , extension , and delineation of borders was selected just before the QRS complex . The length of the left atrial appendage was defined as the distance between the limbus of the left superior pulmonary vein and the apex of the left atrial appendage ; the width of the left atrial appendage was defined as the longest distance between the lateral and ventricular left atrial appendage wall , measured in a line perpendicular to the course of the left atrial appendage curvature ; and the left atrial appendage area was defined as described elsewhere [ 14 ] . For the assessment of intra- and interobserver deviations , left atrial appendage size was measured 1 year after the initial measurement in 20 r and omly selected video recordings by the same observer and in 60 r and omly selected video recordings by three observers from different centers . A thrombus of the left atrium or left atrial appendage was considered definite if at least three of the following five criteria were present : clear borders , echogenicity different from that of surrounding structures , independent mobility , longest diameter greater than 15 mm , and evidence of thrombus in more than one imaging plane [ 15 ] . A second observer from a different center review ed video recordings to confirm diagnosis of thrombus of the left atrium or left atrial appendage . A thrombus was considered probable if only two criteria were present or if the observers disagreed . Spontaneous echocardiographic contrast was diagnosed in the presence of dynamic smoke-like echoes within the left atrium or left atrial appendage with a characteristic swirling motion that was distinct from white noise artifact [ 16 ] . When spontaneous echocardiographic contrast was suspected , the gain setting s were decreased in a stepwise manner to exclude artifact caused by excessive gain . The compression and gain controls were then adjusted to ensure the best possible visualization . Spontaneous echocardiographic contrast was not quantified . A second observer from a different center checked the diagnosis of spontaneous echocardiographic contrast by review ing all video recordings . When the observers disagreed about the presence or absence of spontaneous echocardiographic contrast , the decision made at the time of examination was chosen . This was done because spontaneous echocardiographic contrast was not always visible on review of the video recordings . Outcome Events Primary events were stroke and embolism that extended to viscera or extremities . Stroke was defined as acute onset of a focal neurologic deficit that lasted more than 24 hours and was consistent with a vascular event . Severity and subtypes of stroke were assessed according to established criteria [ 17 ] . Embolism extending to viscera or extremities was defined as a sudden onset of pain that was associated with typical findings on Doppler ultrasonography , angiography , surgery , or autopsy . Secondary events were the need for anticoagulation during follow-up in patients who were primarily receiving aspirin and death not caused by stroke or embolism . Death not caused by stroke or embolism was classified as cardiac or noncardiac on the basis of information from the treating physician and the patient 's family . Follow-up Visits took place 3 , 6 , 12 , 18 , and 24 months after study entry . After a follow-up period of at least 2 years ( ending in February 1994 ) , it was evident that the number of primary outcome events was low . We therefore prolonged the follow-up period and planned further visits , one to be held in 1994 and one to be held in 1995 . Patients who were unwilling or unable to attend the visits were contacted by telephone . Medical records were obtained for patients who had been admitted to a hospital . If a patient had died , an autopsy report or death certificate was obtained . Treatment and Ethical Considerations Although our study was design ed to be observational , we recommended antithrombotic treatment to the patients because of ethical considerations . Because patients with thrombi of the left atrium or left atrial appendage are considered to have a high risk for embolism , we recommended that they receive anticoagulation . The target range for the international normalized ratio was 2.0 to 3.0 , and the treating physicians monitored the ratio [ 5 , 18 ] . We recommended that the remaining patients receive aspirin , 160 mg/d , because preliminary data indicated that aspirin reduces the risk for stroke or embolism in patients with atrial fibrillation [ 19 ] . The institutional review board of the participating centers approved the study . Patients were informed about the background and the procedures of the trial , and informed consent was obtained according to the rules of each center . Statistical Analysis For baseline data , group comparisons were done by analysis of variance for normally distributed data and by the nonparametric Kruskal-Wallis test for data that were not normally distributed . If appropriate , we used the Scheffe post hoc test . The Wilk-Shapiro test was used to check for normality . Contingency table methods , including the chi-square test and the Fisher exact test , were used to analyze categorical data . We used the Cox proportional-hazards model to obtain estimates of relative risk and 95 % CIs for all univariate and multivariate analyses of time-to-event data . All tests were two-sided . The level of significance assumed was an level of 0.05 . We used SAS software ( SAS Institute , Cary , North Carolina ) for analyses . Role of Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data ; did not review the manuscript at any time ; and were not involved in su bmi tting the paper for publication . Results Patients Patients were recruited between January 1990 and February 1992 . Of the 474 Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies --the Whitehall Study of London Civil Servants and the British  Regional Heart Study . The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls . This increased risk confirms that of the other prospect i ve estimate , 5.6 , found in the Framingham study . In the second cohort only one of the men at risk had a stroke , and the risk estimate did not differ significantly from unity . The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study , implying a lesser potential benefit from preventive measures . These lower rates should be considered in the planning of trials . The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease We r and omized 61 patients with paroxysmal atrial fibrillation ( AF ) ( < 48 hours from onset ) to either sotalol or quinidine treatment .  Conversion of rhythm was recorded by Holter monitoring . The starting 80 mg dose of sotalol was repeated at 2 , 6 , and 10 hours if AF persisted ( heart rate > 80 beats/min ) , and if systolic blood was > or = 120 mm Hg . In the quinidine group , if heart rate > 100 beats/min , it was decreased with intravenous digoxin , whereafter 200 mg of oral quinidine sulfate was given maximally 3 times , each dose 2 hours apart . Conversion of AF to sinus rhythm occurred in 17 or 33 patients ( 52 % ) taking sotalol , and in 24 of 28 patients ( 86 % ) taking quinidine ( p < 0.0001 ) . Electric cardioversion was necessary in 39 % of the former and in 14 % of the latter group . The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 + /- 7.6 hours in the sotalol group and 4.0 + /- 2.9 hours in the quinidine group ( p < 0.01 ) . Treatment was discontinued in 16 patients taking sotalol ( 48 % ) because of asymptomatic bradycardia or hypotension , and in 20 taking quinidine ( 71 % ) because of rhythm conversion . Asymptomatic wide complex tachycardia ( QRS > 0.12 second ) was found in 13 % and 27 % of patients taking sotalol and quinidine , respectively . The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups , respectively . Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF . ( ABSTRACT TRUNCATED AT 250 WORDS Summary Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections , using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added . The validity of the simulations was tested in 11 patients with rapid atrial fibrillation .  Serum digoxin concentrations , ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart . In agreement with the predictions of the model , the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group , without any detectable difference in side effects . There were certain discrepancies between the results of the clinical study and the predictions of the model , e.g. in serum digoxin concentrations , perhaps due to impaired clearance in the patients .However , it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation BACKGROUND Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia . Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only . However , there are no prospect i ve data that compare both therapeutic strategies . METHODS The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial was a r and omised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration , which compared rate ( group A , 125 patients ) with rhythm control ( group B , 127 patients ) . In group A , diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation . FINDINGS Over the entire observation period of 1 year , a similar proportion of patients reported improvement in symptoms in both groups ( 76 responders at 12 months in group A vs 70 responders in group B , p=0.317 ) . Amiodarone administration result ed in pharmacological restoration of sinus rhythm in 23 % of patients . Walking distance in a 6 min walk test was better in group B compared with group A , but assessment of quality of life showed no differences between groups . The incidence of hospital admission was higher in group B ( 87 [ 69 % ] out of 127 vs 30 [ 24 % ] out of 125 in group A , p=0.001 ) . Adverse drug effects more frequently led to a change in therapy in group B ( 31 [ 25 % ] patients compared with 17 [ 14 % ] in group A , p=0.036 ) . INTERPRETATION With respect to symptomatic improvement in patients with atrial fibrillation , the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall . However , exercise tolerance is better with rhythm control , although hospital admission is more frequent . These data may serve as a basis to select therapy in individual patients The safety and efficacy of the intravenous ( IV ) calcium channel blocker , verapamil , in controlling the ventricular response or converting to sinus rhythm patients with atrial flutter or atrial fibrillation were assessed . Seventeen patients ( nine with atrial flutter and eight with atrial fibrillation ) with these arrhythmias that were difficult to control pharmacologically were chosen for the study . All patients at the time of study were receiving digoxin .  Either verapamil or placebo was chosen r and omly and a bolus of 0.075 mg/kg ( up to 5 mg ) was administered . Twelve patients had a marked reduction in their ventricular response after IV administration of verapamil ( seven with atrial flutter and five with atrial fibrillation ) . None of these 12 patients converted ( nonconverters ) . The average reduction in heart rate was from 120 + /- 6 beats per minute to a minimum of 83 + /- 13 beats per minute within 20 minutes after drug administration . Verapamil was found to convert five patients with atrial arrhythmias to sinus rhythm ( two with atrial flutter and three with atrial fibrillation ) ( converters ) . In addition , three patients with atrial arrhythmias of less than one month who did not convert with parenteral drug therapy converted within 24 hours while receiving the oral drug . Converters had their supraventricular arrhythmias of significantly shorter duration ( median , three hours v 30 days ) and tended to have smaller left atrial size ( 3.8 + /- 0.7 cm v 4.3 + /- 1.3 cm ) compared with the nonconverters . We conclude that verapamil is safe and effective when administered IV to patients with atrial flutter and fibrillation for control of ventricular response . In short duration atrial arrhythmias , conversion to sinus rhythm is likely once the ventricular response is controlled The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm ( SR ) in patients with paroxysmal atrial fibrillation ( AF ) . The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF ( < 48 hours ) . Seventy-two patients were r and omized to receive 30 mg/kg of either amiodarone or placebo .  Conversion to SR was verified by 24-hour Holter monitoring . Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring . The remaining study groups were comparable ( n = 31 for each ) , except that in the placebo group beta blockers were more common . The patients receiving amiodarone  converted to SR more effectively than those receiving placebo ( p<0.0001 ) . At 8 hours , approximately 50 % of patients in the amiodarone group and 20 % in the placebo group ( Holter successful ) had converted to SR , whereas after 24 hours the corresponding figures were 87 % and 35 % , respectively . The median time for conversion ( 8.7 hours for amiodarone and 7.9 hours for placebo ) did not differ in the groups . Amiodarone was hemodynamically well tolerated , and the number of adverse events in the study groups was similar . Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF The optimal way to convert recent-onset atrial fibrillation to sinus rhythm is a subject of much debate . The effectiveness of intravenous propafenone  has been shown [ 1 - 3 ] , but the full antiarrhythmic effect of this regimen depends not only on the parent compound but on its 5-hydroxylated metabolite [ 4 , 5 ] . This dependence provides a strong rationale for the use of oral loading regimens [ 3 ] . Results of previous controlled studies have shown that oral loading of propafenone is highly effective in converting recent-onset atrial fibrillation to sinus rhythm [ 6 , 7 ] . Safety is a major concern with antiarrhythmic therapy . One of the primary proarrhythmic risks of propafenone and flecainide is the transformation of atrial fibrillation to flutter with 1:1 atrioventricular conduction and hemodynamic impairment [ 8 - 10 ] . We sought to determine whether the effectiveness and safety of propafenone differ in patients who have structural heart disease and patients who do not . Methods From June 1990 to June 1994 , consecutive patients with recent-onset atrial fibrillation ( 7 days ) who presented to one of three centers were considered for enrollment .  Onset of arrhythmia was documented by electrocardiography or by an abrupt onset of palpitations with subsequent evidence of atrial fibrillation on electrocardiography . Patients were excluded for any of the following reasons : age greater than 80 years , heart failure greater than NYHA ( New York Heart Association ) class II , mean ventricular rate during atrial fibrillation less than 70 beats/min , recent myocardial infa rct ion ( within < 6 months ) , unstable angina pectoris , previous or current electrocardiographic evidence ventricular preexcitation or complete bundle-branch block , previous electrocardiographic evidence of second- or third-degree atrioventricular block or bifascicular block , the sick sinus syndrome , hypokalemia ( potassium level < 3.5 mEq/L ) , renal or hepatic failure with severe hypoxia ( Pao 2 < 55 mm Hg ) , severe metabolic disturbances , or known thyroid dysfunction . Patients who were receiving long-term digoxin therapy or antiarrhythmic drugs or had received such treatments within 8 hours before study entry were also excluded . Patients who had atrial fibrillation that lasted 72 hours or longer were enrolled only if they were receiving long-term  warfarin therapy for anticoagulation . Patients provided informed consent . Eligible patients had a 24-hour Holter monitor applied ; after 1 to 2 hours of observation to assess the stability of atrial fibrillation , they were r and omly assigned by center in a single-blind manner to receive propafenone ( 300 mg in two tablets as a single oral dose ) or placebo . All patients received intravenous saline throughout the study period . The electrocardiogram was monitored by telemetry , blood pressure was measured every 2 hours , and 12-lead electrocardiography was done every hour for the first 4 hours and then every 2 hours for the next 4 hours . When patients converted to sinus rhythm , 12-lead electrocardiography was done immediately . Conversion was defined as a stable sinus rhythm that lasted for at least 1 hour . Eight hours after the study drug was administered , physicians could continue treatment with the study drug or switch to a different therapeutic option . Holter monitor tapes were analyzed by two blinded observers using computer scanning systems ( Marquette 8000 , Milwaukee , Wisconsin , and Del Mar Avionics , Irvine , California ) to determine the time of conversion to sinus rhythm and whether an abnormal rhythm was present . Within 24 hours after enrollment , echocardiography was done for each patient and left atrial diameter was measured in the left parasternal long-axis view . On the basis of clinical history and the results of physical examination , echocardiography , and chest radiography , patients were classified as having structural heart disease ( defined as the presence of cardiac abnormalities other than atrial fibrillation ) , hypertension without structural heart disease ( defined as previously recognized systemic hypertension according to the criteria of the World Health Organization ) , or neither . Continuous outcomes and baseline characteristics of the patients were compared by using the chi-square statistic and t-test as appropriate . The rates of conversion to sinus rhythm were assessed at 3 and 8 hours . Odds ratios and corresponding CIs were calculated according to the methods of Gardner and Altman [ 11 ] . We did logistic regression analysis to describe how the interaction of treatment with the presence or absence of heart disease and hypertension affected the probability of conversion to sinus rhythm . Analyses were done using SPS software , version 6.1.3 ( SPS , Inc. , Chicago , Illinois ) . Results Patients During the study period , 407 patients presented to the three centers and were screened for eligibility . Two hundred forty-three patients were eligible , and 240 gave consent . A total of 164 patients were excluded for one or more of the following reasons : age greater than 80 years ( n = 10 ) , heart failure greater than NYHA class II ( n = 33 ) , recent myocardial infa rct ion ( n = 20 ) , bundle-branch block ( n = 24 ) , the sick sinus syndrome ( n = 6 ) , severe hypoxia ( n = 13 ) , thyroid dysfunction ( n = 12 ) , and previous antiarrhythmic treatment ( n = 63 ) . Two hundred forty patients were r and omly assigned to receive propafenone ( n = 119 ) or placebo ( n = 121 ) . The two groups were similar with regard to age , sex , cause of atrial fibrillation , NYHA class , left atrial dimension ( measured by echocardiography ) , structural heart disease , and hypertension ( Table 1 ) . The duration of atrial fibrillation before r and omization ranged from 2.5 to 120 hours and did not differ significantly between the treatment groups . Table 1 . Patient Characteristics Conversion to Sinus Rhythm and Presence of Heart Disease The probability of conversion to sinus rhythm was greater after propafenone than after placebo at 3 and 8 hours ( P < 0.001 ) ( Figure 1 ) . Corresponding odds ratios were 3.8 ( 95 % CI , 2.1 to 6.8 ) at 3 hours and 5.4 ( CI , 3.0 to 9.4 ) at 8 hours . Figure 1 . Conversion to sinus rhythm within 8 hours in patients receiving propafenone or placebo . At 8 hours , the probability of conversion to sinus rhythm was significantly higher in the propafenone group than in the placebo group for patients who had heart disease ( odds ratio , 21.7 [ CI , 5.9 to 80.1 ] ; P < 0.001 ) , patients who had hypertension ( odds ratio , 6.4 [ CI , 2.3 to 17.6 ] ; P < 0.001 ) , and patients who did not have structural heart disease ( odds ratio , 2.8 [ CI , 1.2 to 6.7 ] ; P = 0.02 ) . Conversion rates at 8 hours for patients receiving propafenone were similar among the three heart disease subgroups , but conversion rates for patients receiving placebo differed significantly ( 56 % for patients without structural heart disease , 27 % for patients with hypertension , and 17 % patients with structural heart disease [ P = 0.009 by logistic regression model ] ) . At 3 hours , the probability of conversion to sinus rhythm was higher in the propafenone group than in the placebo group for patients who did not have heart disease ( 48 % for propafenone compared with 26 % for placebo ; odds ratio , 2.6 [ CI , 1.2 to 6.0 ] ; P = 0.02 ) , patients who had hypertension ( 41 % for propafenone compared with 16 % for placebo ; odds ratio , 3.5 [ CI , 1.2 to 10.5 ] ; P = 0.02 ) , and patients who had structural heart disease ( 47 % for propafenone compared with 7 % for placebo ; odds ratio , 12.3 [ CI , 2.5 to 60.5 ] ; P < 0.001 ) . By logistic regression analysis , no significant correlation between heart disease and treatment was seen at 3 hours ( P = 0.2 ) . Mean time SD for conversion to sinus rhythm within 8 hours was 181 118 minutes for propafenone and 181 112 minutes for placebo ( P > 0.2 ) . Adverse Effects Sustained atrial flutter or tachycardia ( lasting 1 min ) occurred in eight patients ( 7 % ) receiving propafenone and seven patients ( 6 % ) receiving placebo ( P > 0.2 ) , regardless of heart disease status . Among these patients , atrioventricular conduction was 2:1 in two patients receiving propafenone ( heart rate , 115 to 140 beats/min ) and three patients receiving placebo ( heart rate , 120 to 150 beats/min ) , 3:1 in six patients receiving propafenone ( heart rate , 60 to 95 beats/min ) and three patients receiving placebo ( heart rate , 60 to 100 beats/min ) , and 1:1 in one patient receiving placebo ( heart rate , 240 beats/min ) . This patient developed atrial flutter and collapsed . Pauses in ventricular rate lasting longer than 2 seconds were seen in one patient ( 1 % ) receiving propafenone and three patients ( 2 % ) receiving placebo ( P > 0.2 ) . Among patients receiving propafenone , nine ( 8 % ) had the following adverse effects : QRS complexes of the electrocardiogram greater than 120 ms ( n = 3 ) , hypotension ( n = 2 ) , slight hypotension and bradycardia at conversion ( n = 3 ) , and phases of junctional rhythm after conversion ( n = 1 ) . No ventricular proarrhythmic effects occurred . Discussion Oral loading of propafenone was effective for conversion to sinus rhythm in our study , as it has been in smaller studies [ 3 , 6 , 7 , 12 , 13 ] . The recent findings of Wijffels and colleagues [ 14 ] in a model of chronic atrial fibrillation in animals indicate that electrophysiologic remodeling occurs within a few hours of persistent atrial fibrillation and results primarily from changes in atrial refractoriness that enhance the persistence of atrial fibrillation . This observation provides a strong rationale for prompt conversion to sinus rhythm . Therefore , oral loading of propafenone ( which has an effectiveness similar to that of intravenous propafenone [ 3 ] ) offers many advantages over such regimens as oral quinidine and intravenous amiodarone , which require titration of dose or a longer period of time to achieve an effect [ 6 , 13 , 15 ] . In controlled trials , propafenone was shown to be more effective and to take effect more quickly than amiodarone [ 13 ] or digoxin plus quinidine [ 6 ] . Intravenous amiodarone  was no more effective than placebo In recent-onset atrial fibrillation , intravenous propafenone has been shown to effectively restore sinus rhythm , whereas the efficacy of intravenous digoxin has been question ed . We directly compared these 2 drugs and placebo in acute atrial fibrillation . One hundred twenty-three patients with atrial fibrillation lasting < 72 hours were r and omized to a 10-minute intravenous infusion of either propafenone ( 2 mg/kg , 41 patients ) or digoxin ( 0.007 mg/kg , 40 patients ) or placebo ( 42 patients ) . After 1 hour , nonconverted propafenone or digoxin patients were switched to the alternative drug , while nonconverted placebo patients were r and omized to either propafenone or digoxin . The observation time ended 1 hour later . By 1 hour , conversion rates were 49 % in the propafenone group , 32 % in the digoxin group ( p = 0.12 ) , and 14 % in placebo group ( p < 0.001 vs propafenone , p = 0.08 vs digoxin ) . After crossover , digoxin converted 5 % of propafenone patients , while propafenone converted 48 % of digoxin patients ( p < 0.05 ) . In the 36 nonconverted  placebo patients , sinus rhythm was obtained in 53 % of cases with propafenone , and in 5 % with digoxin ( p < 0.05 ) . Globally , among the 116 patients who received a drug as first treatment , 30 of 60 patients ( 50 % ) were converted by propafenone versus 14 of 56 ( 25 % ) by digoxin ( p < 0.01 ) ( odds ratio 2.0 , 95 % confidence interval 1.19 to 3.36 ) . In nonconverters , the ventricular rate reduction was faster ( 15 vs 45 minutes ) and more prominent ( -24 % vs -14 % ) with propafenone than with digoxin . In conclusion , intravenous propafenone  terminates atrial fibrillation more effectively than either placebo or intravenous digoxin . In addition , in nonconverted patients , it obtains a more rapid and marked control of the ventricular rate The main goal of this study is to evaluate the safety and efficacy of propafenone versus sotalol as an initial choice of treatment in patients with symptomatic paroxysmal atrial fibrillation ( AF ) , according to a double-blind r and omized system . In the oral propafenone group ( n = 41 ) , 2 patients ( 5 % ) discontinued therapy because of gastrointestinal discomfort in 1 and dizziness in the other . Thirty-one ( 79 % ) of the 39 patients who continued the treatment had effective response to oral propafenone ( > 75 % reduction of symptomatic arrhythmic attacks ) on a mean dose of 663 + /- 99 mg/day with a decrease in attack frequency from 10 + /- 3 to 2 + /- 1 times per week . In the oral sotalol group ( n = 38 ) , 4 patients ( 11 % ) discontinued treatment because of dizziness in 2 and symptomatic bradycardia in 2 . Twenty-six of the 34 patients ( 76 % ) who continued the treatment had effective response to oral sotalol on a mean dose of 200 + /- 57 mg/day with a decrease in attack frequency from 11 + /- 3 to 2 + /- 1 times per week . Comparisons of the results between propafenone and sotalol groups showed a similar incidence of intolerable ( 2 of 41 vs 4 of 38 , p = 0.42 ) and tolerable side effects ( 10 of 39 vs 8 of 34 , p = 1.0 ) . The attack frequency at baseline ( 11 + /- 3 vs 10 + /- 4 times per week , p = 0.23 ) and after treatment ( 3 + /- 1 vs 3 + /- 2 times per week , p = 0.85 ) did not differ significantly between the 2 groups . The incidence of effective response to drugs was also similar ( 31 of 39 vs 26 of 34 , p = 0.78 ) . Furthermore , the decrease of symptom scores ( -32 + /- 8 % vs -29 + /- 7 % , p = 0.18 ) and percentage decrease of ventricular rate ( -15 + /- 4 % vs -18 + /- 4 % , p = 0.10 ) during AF were also similar between the 2 groups . In conclusion , oral propafenone and sotalol are equally effective and safe in preventing attacks and alleviating symptoms of paroxysmal AF Summary Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic altrial fibrillation ( median arrhythmia duration , 5 months ) . After cardioversion , patients were r and omly assigned to receive double-blind propafenone 300 mg tid ( 25 patients ) or disopyramide 250 mg tid ( 31 patients ) . Downward dose adjustment was allowed in case of intolerable side effects . The endpoints were arrhythmia recurrence ; and side effects not amenable to dose reduction . For patients r and omized to propafenone ( mean dose , 878±65 mg/day ) , 66 % [ 95 % confidence interval [ ( CI ) 46–85 % ] and 55 % ( 95 % CI , 34–76 % ) remained in sinus rhythm at 3 and 6 months , respectively ( Kaplan-Meier method ) . Similar figures were found with disopyramide ( mean dose , 704±81 mg/day ) : 71 % ( 95 % CI , 54–87 % ) and 67 % ( 95 % CI , 50–84 % ) at 3 and 6 months , respectively ( p = NS ) . In the patients with a relapse of atrial fibrillation , the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion . However , one patient on disopyramide had an excessively high relapse heart rate ( 170 vs. 100 beats/min ) . Side effects were more frequent on disopyramide . Side effects necessitating drug discontinuation occurred in 12 patients : 4 patients ( 16 % ) on propafenone and 8 ( 26 % ) on disopyramide  . Severe adverse effects occurred in two patients , who developed heart failure while on disopyramide . There were no proarrhythmic events or deaths . Thus , propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation . Propafenone is , however , better tolerated  than disopyramide , which may cause heart failure This study sought to compare the efficacy and safety of intravenous flecainide and sotalol for immediate cardioversion of atrial fibrillation . We performed a prospect i ve , r and omized , single-blind , multicenter trial , including 106 hemodynamically stable patients with atrial fibrillation , stratified according to duration of the arrhythmia . Exclusion criteria included severely reduced left ventricular systolic function , recent antiarrhythmic therapy , and hypokalemia . Patients were r and omly assigned to receive either intravenous flecainide or intravenous sotalol . Trial medication was given at a dose of 1.5 mg/kg body weight ( maximum 150 mg ) . Overall , 28 of 54 patients ( 52 % ) given flecainide and 12 of 52 patients ( 23 % ) given sotalol  converted to sinus rhythm during the first 2 hours after start of the infusion ( p = 0.003 ) . Multivariate analysis confirmed that treatment allocation to flecainide , an arrhythmia duration of < or = 24 hours , higher plasma magnesium level at baseline , higher age for men , and lower age for women independently increases the probability of conversion . The frequency of adverse effects was not significantly different in the 2 treatment groups BACKGROUND Because most strokes cause neurological impairment rather than death , stroke prophylaxis may improve quality of life more than length of life . Thus , an underst and ing of how stroke and stroke prophylaxis affect quality of life is central to clinical decision making for many patients . METHODS We elicited quality -of-life estimates , known as utilities , for 3 degrees of severity of anticipated stroke-mild , moderate , and major- and for stroke prophylaxis with either warfarin sodium or aspirin therapy . We used the time tradeoff and st and ard gamble methods to elicit these utilities from 83 patients who had atrial fibrillation . RESULTS Seventy patients completed the interview successfully . Their utilities for stroke ranged from worse than death ( < 0 ) to as good as current health ( 1.0 ) . The median utilities for mild , moderate , and major stroke were 0.94 , 0.07 , and 0.0 , respectively . Although the median utilities decreased with increasing severity of stroke ( P < .001 ) , there was high interpatient variability within each degree of stroke severity . For example , 7 subjects ( 10 % ) rated a major stroke above 0.5 , while 58 subjects ( 83 % ) rated it as equal to or worse than death . In contrast to the stroke utilities , the median utilities for warfarin and aspirin therapy were high-0.997 and 1.0 , respectively . However , the interpatient variability for warfarin therapy was also important : 11 patients ( 16 % ) with atrial fibrillation rated the utility of warfarin therapy so low that their quality -adjusted life expectancy would be greater with aspirin . CONCLUSION Patients ' utilities for stroke prophylaxis and anticipated stroke vary substantially . Many patients view the quality of life with major stroke as tantamount to or worse than death . These findings highlight the relevance of incorporating patient preferences when choosing stroke prophylaxis BACKGROUND A study was conducted to determine the efficacy and safety of ibutilide fumarate versus placebo in the acute termination of atrial flutter and fibrillation . METHODS AND RESULTS Two hundred sixty-two patients aged 28 to 88 years with atrial flutter or fibrillation duration of 3 hours to 90 days were r and omly assigned in a 5:1 ratio ( ibutilide : placebo ) to receive two 10-minute infusions , 10 minutes apart , of ibutilide ( 1 mg ) or placebo . Patients were hospitalized and monitored by telemetry for 24 hours , with follow-up 72 hours later . Seventy-three ( 34.9 % ) of 209 evaluable ibutilide recipients had termination of atrial flutter or fibrillation within 1.5 hours compared with 0 ( 0 % ) of 41  placebo recipients . Those with atrial flutter had a higher success rate . At hour 24 , 86.3 % remained in normal or alternative sinus rhythm . Of the patients who received ibutilide , 2.3 % experienced drug-related sustained polymorphic or monomorphic ventricular tachycardia and recovered after intervention . Additionally , 7.3 % experienced nonsustained polymorphic or monomorphic ventricular tachycardia . Other frequent medical events in ibutilide recipients were generally also noted in the placebo group . CONCLUSIONS Ibutilide is effective and safe for acute termination of atrial fibrillation or atrial flutter Abstract In new-onset atrial fibrillation ( AF ) , digoxin has a limited ability to control ventricular response , is no better than placebo for facilitating conversion to sinus rhythm , and has a slow onset of action with a narrow toxic-therapeutic ratio . 1,2 Magnesium ( Mg ) has been shown to slow and sometimes normalize the heart rhythm in supraventricular tachyarrhythmias . 3,4 A r and omized trial found Mg prevents  AF in patients after cardiac surgery.5 Because of these factors , we conducted a prospect i ve , r and omized , double-blind , placebo-controlled study addressing whether Mg and digoxin were superior to digoxin alone in controlling the ventricular response of AE Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were r and omised to treatment periods of two weeks on xamoterol ( 200 mg twice daily ) , low dose digoxin , or placebo , in a blind crossover study . The results ( mean SEM ) of symptom scores , a treadmill exercise test , and 24 hour ambulatory electrocardiographic monitoring were obtained . Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin . Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration . Xamoterol , by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate , significantly reduced the difference between the two compared with placebo . In contrast , digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night . Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin . Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity . These changes were translated into symptomatic benefit for the patients studied The effect and choice of a drug to control heart rate for symptomatic improvement in patients with isolated mitral stenosis with normal sinus rhythm ( n = 10 ) or atrial fibrillation ( n = 10 ) were studied . Digoxin ( 0.25 - 0.5 mg daily ) , metoprolol ( 50 - 100 mg twice a day ) and verapamil ( 40 - 80 mg three times a day ) were evaluated for this purpose . An open r and omised cross-over design was followed . The efficacy of a drug was evaluated by : ( 1 ) subjective improvement on a visual analog scale , and ( 2 ) objective improvement on repeated multi-stage symptom-limited treadmill exercise . In patients with sinus rhythm greater than or equal to 50 % subjective improvement was seen in 90 % , 40 % and nil with metoprolol , verapamil and digoxin , respectively . The total work done by these patients was 1008 + /- 541 kpm ( control ) , 2869 + /- 1418 kpm on metoprolol , 2369 + /- 884 kpm on verapamil and 1654 + /- 918 kpm on digoxin . In patients with atrial fibrillation greater than or equal to 50 % subjective improvement was seen in 80 % , 40 % and 30 % with verapamil , metoprolol and digoxin , respectively . The total work done by these patients was 555 + /- 232 kpm ( control ) , 1379 + /- 553 kpm on verapamil , 1251 + /- 575 kpm on metoprolol and 716 + /- 340 kpm on digoxin . The degree of improvement on a drug appeared to be a function of its ability to control resting and exercise heart rates in two different rhythms in these patients . ( ABSTRACT TRUNCATED AT 250 WORDS In patients with recent-onset atrial fibrillation ( AF ) , restoration of sinus rhythm is considered to be the first-line therapeutic option . Although this conversion might be obtained by direct-current shock or intravenous antiarrhythmic drugs , administration of an oral loading dose of class I or III antiarrhythmic drugs is more simple and convenient . This prospect i ve , r and omized , multicenter study compares the time to conversion to sinus rhythm obtained with an oral loading dose of propafenone or amiodarone .  Patients with recent-onset AF ( < 2 weeks ) , without contraindications for the 2 drugs , were r and omly assigned to be treated with propafenone ( 600 mg for the first 24 hours and if necessary a repeated dose of 300 mg for 24 hours ) or amiodarone ( 30 mg/kg for the first 24 hours and if necessary a repeated dose of 15 mg/kg for 24 hours ) . Exact conversion time during the first 24 hours was determined by Holter monitoring . In each treatment group 43 patients with the same baseline characteristics were included . The median time for restoration of sinus rhythm was shorter ( p = 0.05 ) in the propafenone ( 2.4 hours ) than in the amiodarone ( 6.9 hours ) group . After 24 hours ( 56 % in the propofenone and 47 % in the amiodarone group ) and 48 hours , the same proportion of patients in the 2 groups recovered sinus rhythm ( no serious adverse events were noticed ) . Thus , oral loading dose of propafenone or amiodarone was safe with a similar conversion rate of recent-onset AF .  Propafenone had a faster action The safety of a method of outpatient antiarrhythmic drug loading utilizing a continuous loop event recorder was evaluated . The findings suggest that the st and ard 2-day hospital admission for drug loading is not necessary in all patients and a method of outpatient loading may be equally safe OBJECTIVES Our aim was to evaluate the benefits and risks of administering propafenone before electrical defibrillation for chronic atrial fibrillation . BACKGROUND In this context , an antiarrhythmic drug-although potentially useful in preventing early recurrence of arrhythmia-could adversely affect the defibrillation threshold and reduce the cardioversion success rate . METHODS We r and omly assigned 100 patients with chronic atrial fibrillation to oral treatment with either placebo ( 51 patients ) or 750 mg/day of propafenone ( 49 patients ) for 48 h before administration of direct current shock . After successful cardioversion , all patients received propafenone therapy and were followed up for 48 h. RESULTS Before defibrillation , three patients in the propafenone group ( 6.1 % ) had reversion to sinus rhythm and one had sustained ventricular tachycardia . Shock efficacy ( 82.4 % vs. 84.4 % ) and the cumulative effective energy ( 395 + /- 258 vs. 421 + /- 236 J ) were not different between the placebo and propafenone groups . In the propafenone group , 11 patients had their arrhythmia transformed into atrial flutter and required a lower energy level for arrhythmia conversion than did the other patients with continued atrial fibrillation ( 245 + /- 197 vs. 493 + /- 215 J , p < 0.01 ) ; the latter patients showed a trend ( p < 0.10 ) toward higher energy requirements than that of patients who received placebo . The incidence of asymptomatic bradyarrhythmias was higher in the propafenone group ( 28.9 % vs. 7.1 % , p < 0.02 ) , but more patients who received placebo had early recurrence of atrial fibrillation ( 16.7 % vs. 0 % , p < 0.02 ) . Two days after cardioversion , more patients given propafenone ( 73.5 % vs. 52.9 % , p < 0.05 ) were discharged from the hospital with sinus rhythm . During the in-hospital stay , propafenone was withdrawn from six patients ( 6.6 % ) because of side effects . CONCLUSIONS Propafenone , given before electrical cardioversion for chronic atrial fibrillation does not affect the mean defibrillation threshold or the rate of successful arrhythmia conversion . It decreases the recurrence of atrial fibrillation early after shock , thus allowing more patients to be discharged from the hospital with sinus rhythm BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion BACKGROUND Clinical features that consistently predict ischemic stroke in patients with nonvalvular atrial fibrillation have been identified , while echocardiographic risk factors are less well defined . OBJECTIVE To determine whether the results of transthoracic echocardiography add independent information to the clinical risk factors for stroke in patients with atrial fibrillation . METHODS Transthoracic echocardiographic findings and clinical features from 1066 patients with atrial fibrillation assigned to placebo or control in 3 r and omized trials ( Boston Area Anticoagulation Trial for Atrial Fibrillation , Stroke Prevention in Atrial Fibrillation I Study , and Veterans Affairs Prevention in Atrial Fibrillation Study ) were correlated with subsequent ischemic stroke by multivariate analysis . RESULTS The mean + SD age of patients was 67 + /- 10 years , 78 % were men , 55 % had a history of hypertension , 19 % had a history of diabetes , 7 % had a previous transient ischemic attack or stroke , and 27 % had a history of heart failure . During a mean follow-up of 1.6 years , 78 ischemic strokes occurred ( annual rate , 4.7 % ) . Moderate to severe left ventricular systolic dysfunction shown via 2-dimensional echocardiography was a strong independent predictor of stroke ( relative risk , 2.5 ; P<.001 ) in the 1010 patients in whom echocardiographic values for left ventricular function were available . Left atrial diameter by M-mode echocardiography did not predict stroke ( relative risk , 1.02/mm ; P = .10 ) . Of 163 patients categorized as low risk based on clinical features ( annual stroke rate , 0.8 % ; 95 % confidence interval , 0.2%-3.0 % ) , 10 had moderate to severe left ventricular dysfunction shown via 2-dimensional echocardiography and a 9.3 % per year risk of stroke ( 95 % confidence interval , 1.3%-66 % ) . Conversely , 728 of the 847 patients at high risk for stroke based on clinical criteria had normal or mildly abnormal left ventricular function ; their stroke rate was 4.4 % ( 95 % confidence interval , 3.4%-5.8 % ) . CONCLUSIONS Left ventricular systolic dysfunction shown via 2-dimensional transthoracic echocardiography independently predicts risk of stroke in patients with atrial fibrillation . Echocardiography may prove most useful in a small group of patients who have a low risk of stroke according to clinical factors Nadolol , a long-acting beta-adrenergic-blocking agent , was evaluated in 20 patients with chronic atrial fibrillation by means of a r and omized , double-blind , crossover study . Patients were required either to demonstrate resting heart rates in excess of 80 bpm or to show a rate of 120 bpm or an increment of greater than 50 bpm during mild treadmill exercise provocation ( 3 minutes , 1.75 mph , 10 % grade ) . With placebo the group averaged a heart rate of 92 + /- 19 bpm , determined by 24 hours of ambulatory ECG recordings ; this rate was significantly reduced to 73 + /- 16 bpm ( p less than 0.001 ) with nadolol ( mean dosage , 87 + /- 43 mg/day ) . During st and ardized exercise testing , heart rates increased to 153 + /- 26 bpm with placebo and to 111 + /- 24 bpm with nadolol ( p less than 0.001 ) , representing 65 % and 52 % increments , respectively .  Digoxin blood levels averaged 0.8 + /- 0.5 ng/ml with placebo and were similar with nadolol ( 0.9 + /- 0.4 ; p = NS ) . Total exercise time on a modified Bruce treadmill protocol was 466 + /- 143 seconds with placebo and was significantly decreased by nadolol ( 380 + /- 143 ; p less than 0.01 ) . During initial dose titration with nadolol , one patient was dropped from study for intolerable fatigue and one for worsened claudication . No patients were dropped from the double-blind treatment periods , although two patients receiving nadolol and one patient receiving placebo complained of moderate fatigue . We conclude that nadolol is a safe and effective agent for the control of spontaneous and exercise-provoked heart rates in patients with chronic atrial fibrillation who were already receiving digoxin treatment Background : The management of permanent atrial fibrillation ( PAF ) consists primarily of long‐term anticoagulation with either aspirin or warfarin to prevent systemic embolization , and modulation of ventricular rate ( VR ) to improve cardiac function by prolonging the ventricular diastolic filling time OBJECTIVES This study was design ed to test the hypothesis that conversion of atrial flutter in humans by ibutilide , a new class III antiarrhythmic agent , is characterized by an increase in atrial cycle length variability . BACKGROUND Conversion of tachyarrhythmias has been associated with increased oscillations of cycle length . METHODS Electrograms and monophasic action potentials from the right atrium in 35 patients with spontaneous , sustained atrial flutter were recorded before , during and after  intravenous ibutilide ( 0.005 to 0.025 mg/kg body weight , n = 25 ) or placebo ( n = 10 ) . Atrial cycle length , cycle length variability ( coefficient of variation ) , diastolic interval and diastolic interval variability were measured from 10 consecutive cycles at baseline and 3 min before , 1 min before , 30 s before and immediately before conversion . Similar measurements were made in patients who received ibutilide or placebo but did not convert . RESULTS Ibutilide  converted atrial flutter in 14 of 25 patients 25 + /- 16 min ( mean + /- SD ) after initiation of the infusion , whereas placebo converted no patients . Atrial cycle length was prolonged to the same extent in ibutilide converters and nonconverters ( 36 + /- 19 vs. 38 + /- 21 ms , p = NS ) and was not affected by placebo .  Beat-to-beat variability in atrial cycle length ( baseline 1.2 + /- 0.7 vs. preconversion 7.3 + /- 4.9 , p < 0.01 ) and diastolic interval ( baseline 11 + /- 8 vs. preconversion 33 + /- 23 , p < 0.05 ) increased significantly just before atrial flutter conversion and remained unchanged in ibutilide nonconverters and placebo group patients . CONCLUSIONS Ibutilide prolongs atrial cycle length , but conversion of atrial flutter by ibutilide is characterized by increased variability in atrial cycle length and diastolic interval The effects of two calcium channel blockers , diltiazem ( 270 mg/day ) and verapamil ( 240 mg/day ) , were studied in 18 patients with chronic atrial fibrillation . During 24 h Holter electrocardiographic monitoring , mean ventricular rate ( beats/min ) decreased from 88 + /- 14 with placebo to 76 + /- 13 ( p less than 0.001 ) with diltiazem and 80 + /- 11 ( p less than 0.01 ) with verapamil .  Maximal symptom-limited exercise tolerance ( W ) increased from 127 + /- 39 during the placebo period to 136 + /- 42 ( p less than 0.01 ) with diltiazem and 137 + /- 39 ( p less than 0.01 ) with verapamil .  Ventricular rate and rate-pressure product were lower at rest and during exercise with diltiazem and verapamil than with placebo ( p less than 0.001 ) , with the drugs being similarly effective . Ventricular rate at maximal exercise ( beats/min ) was 179 + /- 13 with placebo compared with 159 + /- 21 with diltiazem and 158 + /- 23 with verapamil . Maximal oxygen uptake ( ml/kg per min ) was 22.3 + /- 4.5 with placebo , 23.7 + /- 4.9 ( p less than 0.05 ) with diltiazem and 22.9 + /- 4.5 with verapamil ( p = NS ) . Respiratory gas exchange anaerobic threshold was reached at a work load ( W ) of 76 + /- 21 with placebo , 84 + /- 27 ( p less than 0.05 ) with diltiazem and 85 + /- 23 ( p less than 0.01 ) with verapamil . In conclusion , patients with chronic atrial fibrillation have modestly improved exercise tolerance with calcium channel blockade therapy . The dromotropic responses and the effects on physical performance are of similar magnitude for diltiazem and verapamil Beta-adrenergic blocking agents are useful in controlling excessive ventricular rate in chronic atrial fibrillation ( AF ) but often reduce exercise capacity . To investigate the advantage of labetalol -- a unique beta blocker with alpha-blocking property -- in chronic AF , 10 patients without underlying structural heart disease were studied with treadmill test , 12-minute walk and 24-hour ambulatory electrocardiographic monitoring . Patients were r and omized and crossed over to receive 4 phases of treatment  ( placebo , digoxin , digoxin with half-dose labetalol , and full-dose labetalol ) . Exercise duration s were 14.1 + /- 1.5 , 14.2 + /- 1.5 , 16.1 + /- 1.1 and 15.6 + /- 1.1 minutes , respectively , indicating that labetalol did not reduce exercise tolerance . Although digoxin had no advantage over placebo in controlling maximal heart rate ( 177 + /- 2 vs 175 + /- 3 beats/min ) , labetalol , both as monotherapy or as an adjunct to digoxin , was advantageous ( 156 + /- 4 vs 177 + /- 2 beats/min , p less than 0.01 , and 154 + /- 4 vs 177 + /- 2 beats/min , p less than 0.01 , respectively ) . The rate-pressure product was consistently lowered by labetalol at rest and during exercise . At peak exercise , the addition of labetalol to digoxin reduced the maximal rate-pressure product achieved from 30,900 + /- 1300 to 24,100 + /- 2,000 mm Hg/min ( p less than 0.01 ) and the maximal rate-pressure product was lowest with full-dose labetalol ( 22,300 + /- 1,600 mm Hg/min ) . During submaximal exercise on treadmill or during the 12-minute walk , the combination of labetalol and digoxin produced the best heart rate control , whereas labetalol monotherapy was comparable to digoxin therapy . ( ABSTRACT TRUNCATED AT 250 WORDS Magnesium has previously been used in the treatment of various arrhythmias , but few r and omized and prospect i ve studies are available . In a single‐blind study , the efficacy and safety of intravenous magnesium sulfate ( bolus doses of 5 + 5 mmol followed by infusion of 0.04 mmol/min ) versus verapamil ( 5 + 5 mg followed by 0.1 mg/min ) was evaluated in 57 patients with supraventricular arrhythmias ( supraventricular tachycardia , atrial fibrillation , and atrial flutter ) of recent onset ( less than 1 week ) . Fifteen ( 58 % ) of the patients receiving magnesium ( n = 26 ) converted to sinus rhythm within 4 h , and 16 ( 62 % ) within 24 h. Verapamil  caused a lower ventricular rate , but only six ( 19 % ) of the patients ( n = 31 ) converted to sinus rhythm within 4 h ( p < 0.01 ) and 16 ( 52 % ) within 24 h ( NS ) . No side effects were observed during magnesium infusion , whereas six patients receiving verapamil had to be withdrawn from further study medication due to symptomatic side effects ( hypotension in three , cardiac failure in three ) . Magnesium appears to be an effective and safe drug for the treatment of supraventricular arrhythmias . The overall efficacy for conversion to sinus rhythm is at least as effective as with verapamil , and its action is more rapid In a r and omized , double-blind , controlled study of 98 patients with atrial fibrillation ( AF ) ( present for > or = 30 minutes , < or = 72 hours , and a ventricular response of > or = 100 beats/min ) , intravenous flecainide ( 2 mg/kg , maximum 150 mg ) was compared with intravenous amiodarone ( 7 mg/kg ) and placebo .  Exclusion criteria included significant left ventricular dysfunction , inotrope dependence , recent antiarrhythmic therapy , hypokalemia , and pacemaker dependence . Reversion to stable sinus rhythm within 2 hours of starting medication was considered likely to be due to drug effect . Twenty of 34 patients ( 59 % ) given flecainide , 11 of 32 ( 34 % ) given amiodarone , and 7 of 32 ( 22 % ) given placebo reverted to stable sinus rhythm in < or = 2 hours after starting medication ( chi-square 9.87 , p = 0.007 ) . More patients reverted to stable rhythm with flecainide than with placebo ( p = 0.005 ; odds ratio 5.1 , 95 % confidence interval 1.54 to 17.5 ) . There was no significant difference between amiodarone and placebo or between flecainide and amiodarone . However , after 8 hours there were no significant differences in reversion between the treatment groups : flecainide ( n = 23 , 68 % ) , amiodarone ( n = 19 , 59 % ) , and placebo ( n = 18 , 56 % ) . Amiodarone promptly reduced the ventricular rate , and this effect was maintained for 8 hours in those whose reversion to stable sinus rhythm was unsuccessful : flecainide was no more effective than placebo in controlling ventricular rate . Adverse effects were not significantly different in the 3 groups . Thus , intravenous flecainide results in earlier reversion of AF than does intravenous amiodarone or placebo . Amiodarone , although less effective in reverting AF , slows the rapid ventricular response . ( ABSTRACT TRUNCATED AT 250 WORDS In a prospect i ve , single-blind trial , we r and omized 150 consecutive symptomatic patients with acute ( < or = 48 hours ' duration ) atrial fibrillation to receive intravenous flecainide , propafenone , or amiodarone . Flecainide and propafenone were administered as a bolus dose of 2 mg/kg in 20 minutes . A second bolus dose of 1 mg/kg in 20 minutes was administered if conversion to sinus rhythm was not achieved after 8 hours . Amiodarone was administered as a bolus of 5 mg/kg in 20 minutes followed by a continuous infusion of 50 mg/hour . By the end of a 12-hour observation period , conversion to sinus rhythm was achieved in 45 patients ( 90 % ) in the flecainide group , 36 ( 72 % ) in the propafenone group , and 32 ( 64 % ) in the amiodarone group ( p = 0.008 for the overall comparison , p = 0.002 for flecainide vs amiodarone , p = 0.022 for flecainide vs propafenone , and p = 0.39 for propafenone vs amiodarone ) . When compared with amiodarone , this higher reversion rate with flecainide was present from the first hour of the study period . However , only after administering the second bolus was there a significant difference between flecainide and propafenone .  Median time to conversion to sinus rhythm was different among groups ( p < 0.001 ) , and it was lower in the flecainide ( 25 minutes ; range 4 to 660 ) and propafenone ( 30 minutes ; range 10 to 660 ) groups than in the amiodarone group ( 333 minutes ; range 15 to 710 ; p < 0.001 for both comparisons ) . Flecainide , at the doses administered in this study , is more effective than propafenone and amiodarone for conversion of acute atrial fibrillation to sinus rhythm .  Propafenone and amiodarone have similar conversion rates , although propafenone was faster in achieving the conversion to sinus rhythm A population of 105 patients with recent onset ( < 72 h ) atrial fibrillation was r and omly treated with propafenone as a single oral loading dose of 450 mg ( Regimen A ) or 600 mg ( Regimen B ) or with placebo . A 24-h Holter was performed . Criteria of efficacy were conversion to sinus rhythm at 2 , 4 and 8 h compared to placebo and also significant reduction of mean ventricular rate in persistent atrial fibrillation . After 2 h , regimen B was more effective than either regimen A ( 43 % vs. 8 % ; p = 0.001 ) or placebo ( 11 % ; p = 0.004 ) . At 4 h , both the active treatments were more effective than placebo ( 17 % vs. 46 % regimen A and 57 % vs. regimen B ; p < 0.04 and p < 0.001 , respectively ) . Sinus rhythm resumed within 24 h in 71 % , 80 % and 69 % of the patients with regimen A , B and placebo , respectively ( p = not significant ) . The mean ventricular rate reduction after 1 h was 8 % , 11 % and 4 % for regimen A , B and placebo , respectively ( p < 0.005 vs. regimen B ) , and 17 % , 25 % and 6 % respectively ( p < 0.001 placebo vs. regimen A and B , p < 0.05 regimen B vs. A ) at 2 h. No major adverse effect occurred . Atrial flutter with 1:1 atrioventricular conduction only in one case who received placebo . Propafenone acute oral administration is more effective than placebo in rapidly converting recent-onset atrial fibrillation to sinus rhythm and may be the treatment of choice in this setting limiting hospitalization and contributing to improved quality of life Fifty-three patients with chronic atrial fibrillation participated in a r and omized cross-over trial in order to compare the ability of two drug regimens to establish and maintain sinus rhythm . The patients were given orally either sustained release quinidine 0.4 g twice day or verapamil 80 mg three times a day . Thirty-one patients tried both regimens . Quinidine was found to have a greater ability to induce conversion to sinus rhythm by drug alone ( p less than 0.05 ) and also a greater ability to maintain sinus rhythm after conversion ( after 3 months p less than 0.05 ) . There was , however , also a significantly larger proportion of patients on quinidine who were withdrawn from the study due to side effects and two patients on quinidine  died outside hospital . The study indicate that quinidine is somewhat superior to verapamil both in the establishing and preserving of sinus rhythm in subjects who are able to tolerate the drug To assess the cardiac and extracardiac safety and efficacy of flecainide versus propafenone in patients suffering from episodes of paroxysmal atrial fibrillation ( AF ) or atrial flutter , 97 patients were enrolled in a r and omized , open-label , long-term , parallel , comparative multicenter study . The diagnosis of paroxysmal AF or atrial flutter had to be fully documented prior to inclusion in the study . Of the 97 patients enrolled in the study , 48 patients ( 25 men , 23 women , mean age 62.4 + /- 12.3 years ) received flecainide ; 49 patients ( 26 men , 23 women , mean age 63.6 + /- 12.2 years ) received  propafenone . The initial dose of flecainide was 50 mg twice daily , and this could be increased in steps of 50 mg twice daily every 4 days to a maximum of 300 mg/day . The initial dose of propafenone was 300 mg twice daily and this could be increased in steps of 300 mg every 4 days to a maximum of 1200 mg/day . At each visit , medical events , vital sign measurements ( blood pressure , pulse rate ) , concomitant medications , adverse experiences , and study drug dosage changes were evaluated . Routine clinical laboratory tests were evaluated at the month 6 visit , and a 24-hr Holter recording was obtained at the month 1 visit . Almost half ( 45 ) of the patients were discontinued from the study before completing 1 year of therapy . The probability of successful treatment versus time -- i.e . , the proportion of patients who remained on therapy over the course of 1 year therapy -- was 0.619 for the flecainide group and 0.469 for the propafenone group ( p = 0.079 ; difference not significant ) . The difference is largely attributed to the higher proportion of patients in the propafenone group ( 9 ) than in the flecainide group ( 2 ) who experienced side effects important enough to stop the treatment . ( The incidence of side effects was not statistically different between treatment groups , although it was higher in the propafenone group . ) The proportion of patients who discontinued treatment due to inadequate response was similar in the 2 groups : 11 patients ( 22.9 % ) in the flecainide group and 12 patients ( 24.4 % ) in the propafenone group withdrew from the study , primarily because of an inadequate response , i.e. , they experienced an increase in duration , frequency , and severity of attacks of AF or atrial flutter . Neurologic signs , central and peripheral , were mostly encountered in the flecainide group ( 8.5 % ) , and , gastrointestinal effects were more often reported in the propafenone group ( 16.7 % ) . In paroxysmal AF and paroxysmal atrial flutter , flecainide and propafenone are equally effective . However , in this study the probability of a patient 's staying on flecainide after 1 year had a tendency to be higher than the probability of staying on propafenone , due to a greater proportion of secondary effects with propafenone To evaluate the efficacy of propafenone in converting recent‐onset atrial fibrillation ( AF ) lasting < 7 days , 182 patients were treated intravenously with propafenone ( Group 1 , n = 98 ) and with placebo 0.9 % saline solution ( Group 2 , n = 84 ) in a double blind study . The treatment was continued until sinus rhythm ( SR ) was restored , but for no more than 24 h. Eighty‐nine patients treated with propafenone ( 90.8 % ) and 27 patients treated with placebo ( 32.1 % ) responded to the treatment and SR was restored ( p < 0.0005 ) . The mean time for SR restoration was 2.51± 2.77 h in Group 1 , and 17.15± 7.8 h in Group 2 ( p < 0.0005 ) . In both groups the patients in whom SR was not restored ( nonresponders ) had larger left atrial size and longer duration of AF than responders at the onset of the arrhythmia . Nonresponders in Group 1 showed a decrease in mean ventricular rate ( MVR ) from 143± 16 to 101± 18 ( p < 0.0005 ) , while in the nonresponders in Group 2 no reduction of MVR was observed . Two patients whose SR was restored with propafenone had sinus st and still lasting 3.4 and 3.8 s , respectively . Propafenone used intravenously is an effective , quick , and safe drug for treating AF . Moreover , it significantly reduces MVR in nonresponders In a single-blind r and omized study , the efficacy and safety of intravenous propafenone ( 2 mg/kg body weight per 10 min ) versus flecainide ( 2 mg/kg per 10 min ) were assessed in 50 patients with atrial fibrillation or flutter . Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 ( 55 % ) of 20 patients with atrial fibrillation treated with propafenone and in 18 ( 90 % ) of 20 with atrial fibrillation treated with flecainide ( p less than 0.02 ) . If atrial fibrillation was present less than or equal to 24 h , conversion to sinus rhythm was achieved in 8 ( 57 % ) of 14 patients in the propafenone group and 13 ( 93 % ) of 14 in the flecainide group ( p less than 0.05 ) . Atrial flutter was converted in two ( 40 % ) of five patients treated with propafenone and in one ( 20 % ) of five with flecainide ( p = NS ) . Mean time to conversion was 16 + /- 10 min in the propafenone group versus 18 + /- 13 min in the flecainide group ( p = NS ) . QRS lengthening ( 83 + /- 15 to 99 + /- 20 ms ) was observed only in the patients treated with flecainide ( p less than 0.001 ) . Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm . Transient adverse effects were more frequent in the flecainide group ( 40 % ) than in the propafenone group ( 8 % ) ( p less than 0.01 ) . In conclusion , at a dose of 2 mg/kg in 10 min , flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm . However , considering the propafenone plasma levels and very few adverse effects , the dose or infusion rate , or both , used in the propafenone group may not have been sufficient to achieve an optimal effect . Neither drug seems very effective in patients with atrial flutter The efficacy and safety of flecainide were studied in the maintenance of sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter . Eighty-one patients were r and omized to flecainide treatment or no treatment .  Baseline characteristics of both groups were comparable . Compared to previous studies , patients could be classified as difficult-to-treat patients . Multiple regression analysis showed New York Heart Association class I for exercise tolerance ( p = 0.0004 ) and flecainide treatment ( p = 0.01 ) to be the main factors increasing the arrhythmia-free episode . However , Mantel-Cox lifetable analysis did not reveal significant differences between arrhythmia-free survival curves of both treatment groups . In the flecainide-treated group , 9 % of patients experienced side effects , mostly related to negative dromotropic effects . The incidence of ventricular proarrhythmia in this group of patients was low . Thus , flecainide may be effective in postponing arrhythmia recurrence , even in difficult-to-treat patients . Caution should be excercised in treating patients with underlying conduction disturbances , sick sinus syndrome or characteristics favoring development of ventricular proarrhythmia Summary : Thirty-four patients with atrial fibrillation complicating suspected acute myocardial infa rct ion were r and omised to treatment with intravenous amiodarone ( n = 18 ) or intravenous digoxin ( n = 16 ) . After 24 h , similar proportions of patients in each group had reverted to sinus rhythm . However , there was a tendency towards earlier reversion with amiodarone . At 4 h , 72 % of the amiodarone group had reverted to sinus rhythm , compared with 31 % of the digoxin group ( p < 0.1 ) . This tendency was more marked in patients with definite infa rct ion ( at 4 h , amiodarone 75 % reversion , digoxin 10 % reversion ) . Neither drug had a significant effect on blood pressure . Atrial fibrillation may cause serious haemodynamic deterioration in acute myocardial infa rct ion . In comparison with digoxin , amiodarone offers more rapid control of the ventricular response rate and may , in addition , restore sinus rhythm more rapidly The effect of the combined treatment with propranolol 20 mg tid and diltiazem 60 mg tid in patients with chronic atrial fibrillation treated with digoxin  was evaluated . Thirteen patients entered a double‐blind , three‐phase crossover study . Heart rate was significantly reduced during rest and at maximal exercise ( p < 0.05 ) during combined treatment compared with treatment with any single drug . No significant changes in maximal work load , exercise time , systolic blood pressure at maximal work load , or subjective sensation of well‐being could be demonstrated during combined drug treatment . The RR distribution pattern was unaffected by the addition of propranolol , diltiazem , or their combination to the chronic digoxin treatment . It is concluded that the combination of diltiazem and propranolol has no advantages over any of these drugs singly , in the moderation of heart rate in patients with atrial fibrillation even combined with basic digitalis treatment , and that the intrinsic AV nodal function is unaffected by these drugs or their combination BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients UNLABELLED The efficacy and safety of intravenous propafenone , amiodarone , or placebo were compared in the treatment of atrial fibrillation ( AF ) of recent onset ( duration < or = 48 hours ) . METHODS 143 patients ( 77 men , mean age 63 + /- 12 years ) were studied , of whom 46 received propafenone ( 2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours ) , 48 received amiodarone ( 300 mg intravenously over 1 hour , followed by 20 mg/kg over the next 24 hours , plus 1,800 mg/day orally , in 3 divided doses ) , and 49 received placebo ( the equivalent amount of saline i.v . over 24 hours ) . Digoxin was administered to all patients who had not previously received it . RESULTS Conversion to normal sinus rhythm occurred in 36 of 46 patients ( 78.2 % ) receiving propafenone , in 40 of 48 patients ( 83.3 % ) receiving amiodarone , and in 27 of the 49 ( 55.10 % ) controls ( P < 0.02 , drug vs placebo , between drugs NS ) . The mean time to conversion was 2 + /- 3 hours for propafenone , 7 + /- 5 hours for amiodarone , and 13 + /- 9 for placebo ( P < 0.05 ) . Patients who converted had smaller atria than those who did not ( diameter : 42.7 + /- 5 vs 47.2 + /- 7 mm , P < 0.001 for all ) . Treatment was discontinued in one patient in the amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening . No side effects were observed in the placebo group . CONCLUSIONS Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm . However , propafenone offered the advantage of more rapid conversion than amiodarone Fourteen patients ( four females ) with chronic atrial fibrillation were entered into a r and omized , double-blind crossover study to compare the effects of treatment with diltiazem alone , digoxin alone , and a combination of diltiazem plus digoxin . The dose of digoxin was adjusted so as to achieve serum concentrations within the range 1.3 - 2.6 nmol l-1 between six and eight hours after dosing . Four patients were withdrawn from the study ; three patients experienced side effects while taking diltiazem and one reverted to sinus rhythm while taking digoxin . Among the remaining 10 patients , mean heart rates were significantly lower during treatment with the combination of digoxin and diltiazem than with digoxin alone both at rest , after exercise and during ambulatory ECG monitoring . Post-exercise heart rates were reduced by 15 % with combination therapy when compared with digoxin alone ( 151.9 vs. 128.1 bpm ) , but there was no evidence that this reduction in ventricular rate was associated with improved exercise tolerance . The results suggest that further reduction of the rapid ventricular rates seen in digitalized patients with AF by the use of diltiazem does not appear to be of benefit in the majority of patients Sixty-two patients with recent-onset ( less than or equal to 1 week ) atrial fibrillation ( New York Heart Association functional class 1 and 2 ) were r and omized in a single-blind study to 1 of the following treatment groups : ( 1 ) flecainide ( 300 mg ) as a single oral loading dose ; or ( 2 ) amiodarone ( 5 mg/kg ) as an intravenous bolus , followed by 1.8 g/day ; or ( 3 ) placebo for the first 8 hours . Twenty-four-hour Holter recording was performed , and conversion to sinus rhythm at 3 , 8 , 12 and 24 hours was considered as the criterion of efficacy . Conversion to sinus rhythm was achieved within 8 hours ( placebo-controlled period ) in 20 of 22 patients ( 91 % ) treated with flecainide , 7 of 19 ( 37 % ) treated with amiodarone ( p less than 0.001 vs flecainide ) , and 10 of 21 ( 48 % ) treated with placebo ( p less than 0.01 vs flecainide ) . Resumption of sinus rhythm within 24 hours occurred in 21 of 22 patients ( 95 % ) with flecainide and in 17 of 19 ( 89 % ) with amiodarone ( p = not significant ) . Mean conversion times were shorter for flecainide ( 190 + /- 147 minutes ) than for amiodarone ( 705 + /- 418 ; p less than 0.001 ) . No major side effects occurred . At Holter monitoring , a pause of 9.3 seconds was observed in 1 asymptomatic patient treated with flecainide . Phases of atrial flutter with a ventricular rate less than or equal to 150 beats/min were detected before sinus conversion in 1 patient receiving placebo and in 2 receiving flecainide . ( ABSTRACT TRUNCATED AT 250 WORDS Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3 - 1.8 , international normalised ratio 2.0 - 4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel r and omised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation Twenty digitalized elderly patients with chronic atrial fibrillation were r and omized into a double-blind cross-over study . None was in overt heart failure and all were taking < 80 mg frusemide daily . They received xamoterol 200 mg b.d . for 2 months with their usual dose of digoxin for 1 month and placebo digoxin for the other month . Twenty-four-hour heart rate analysis was done at baseline and at the end of each treatment period . Compared with baseline digoxin , xamoterol alone significantly increased nocturnal minimum heart rate [ 85 + /- 17 vs. 62 + /- 9 ( mean + /- SD ) , p < 0.0001 ] without affecting daytime maximum heart rate ( 132 + /- 18 vs. 122 + /- 20 , p = NS ) . Compared with baseline digoxin , xamoterol plus digoxin significantly increased nocturnal minimum heart rate ( 68 + /- 8 , p < 0.05 ) and reduced daytime heart rate ( 114 + /- 17 , p < 0.05 ) . The mean number of pauses > 1.5 s was significantly reduced by xamoterol alone . Walking distance in 6 minutes was 406.1 + /- 27.1 m ( mean + /- SE ) at baseline and improved significantly on both treatments ( 450.3 + /- 19.8 on xamoterol ; p < 0.02 and 453.7 + /- 19.2 on xamoterol plus digoxin ; p < 0.01 ) . No significant change was found in subjective measurements of palpitations , breathlessness and well-being using visual analogue scales .  Xamoterol combined with digoxin improves effort tolerance and heart-rate control by reducing diurnal tachycardia and nocturnal bradycardia and pauses OBJECTIVES The primary objective was to evaluate the usefulness of transesophageal echocardiography (TEE)-guided cardioversion to prevent thromboembolic complications in patients with atrial fibrillation ( AF ) and effective anticoagulation ( International Normalized Ratio of 2 or 3 ) at least three weeks before cardioversion . BACKGROUND Transesophageal echocardiography has been proposed as a method of screening patients for left atrial thrombi before direct-current cardioversion of AF . The usefulness of TEE as a screening tool has always been evaluated in patients without long-term anticoagulation before cardioversion . METHODS This prospect i ve , single-center , observational study , performed on an intention-to-cardiovert basis , comprised 1,076 consecutive , unselected patients with AF . The initial two years were design ed to be the control phase , during which the conventional approach was used . After that , cardioversion guided by TEE was performed in consecutive patients . RESULTS The prevalence of left atrial thrombi was 7.7 % in patients with persistent AF and effective anticoagulation . During the first four weeks after electrical cardioversion , six thromboembolic complications were observed in patients in whom the TEE-guided approach was employed ( 6 [ 0.8 % ] of 719 patients ) , compared with three thromboembolic complications in patients in whom the conventional approach was used ( 3 [ 0.8 % ] of 357 patients ) . None of the patients in whom electrical cardioversion was not performed experienced an embolic event . CONCLUSIONS There were no differences in the rate of embolic events between the two treatment groups . In patients with AF and effective anticoagulation , TEE-guided electrical cardioversion does not reduce the embolic risk . However , TEE revealed left atrial thrombi in 7.7 % of patients with AF and effective anticoagulation , before direct-current cardioversion BACKGROUND The clinical presentation and causes of  atrial fibrillation ( AF )  in the 1990s may differ from AF seen 2 to 3 decades ago . It was the objective of this prospect i ve study to characterize various clinical presentations and underlying conditions of patients with AF observed in general practice in France . METHODS AND RESULTS The study population comprised 756 patients ( 19 to 95 years of age ) with electrocardiographically documented AF subdivided into paroxysmal ( < 7 days ) , chronic ( last episode > 1 month ) and recent onset AF(persistent > 7 days and < 1 month ) .  Symptoms were present in 670 patients ( 88.6 % ) . The relative prevalences of paroxysmal , chronic , and recent onset AF were 22.1 % , 51.4 % , and 26.4 % , respectively . Cardiac disorders , present in 534 patients ( 70.6 % ) , included hypertension ( 39.4 % ) , coronary artery disease ( 16.6 % ) , and myocardial diseases ( 15.3 % ) as the most common . Rheumatic valvular disease represented a common cause in women ( 25 . 0 % ) but not in men ( 8.0 % ) . The paroxysmal group differed by a high percentage of palpitations ( 79.0 % ) and a low percentage of underlying heart disease ( 53.9 % ) . With a mean follow-up of 8.6+/-3.7 months , 28 patients ( 3.7 % ) died , including 6 fatal cerebrovascular accidents . Among the 728 patients who survived , congestive heart failure occurred in 30 patients ( 4.1 % ) , and embolic complications occurred in 13 patients ( 1.8 % ) . In the paroxysmal AF group , 13 patients ( 8.0 % ) developed chronic AF and 51 ( 31.3 % ) had AF recurrences . At the time of follow-up , 53 patients ( 14.3 % ) from the chronic AF group and 108 patients ( 55.7 % ) from the recent onset AF group were in sinus rhythm . CONCLUSIONS This large-scale study establishes the current demographic profile of out-of-hospital patients with AF and highlights some of the changes that have occurred in the past decades , including a particular shift in cardiac causes toward nonrheumatic AF . This study also demonstrates significant differences between various subsets of AF OBJECTIVES This study compared the efficacy and safety of sotalol and quinidine for conversion and prevention of recurrent  atrial fibrillation .  BACKGROUND Atrial fibrillation is the most common arrhythmia . Pharmacologic therapy has been advocated for both immediate restoration of sinus rhythm and prevention of recurrent atrial fibrillation .  Quinidine is the therapeutic mainstay for both purpose s , but its safety has recently been question ed . Although sotalol has been used successfully to maintain sinus rhythm after direct current cardioversion , its efficacy in pharmacologically reverting atrial fibrillation has not been examined . METHODS Fifty consecutive patients with persistent atrial fibrillation were r and omized to receive quinidine or sotalol for up to 7 days to restore sinus rhythm . Patients were followed up for 6 months . RESULTS Quinidine was more effective than sotalol in terminating atrial fibrillation ( 60 % vs. 20 % , p = 0.009 ) . When nonresponders to drug therapy underwent subsequent direct current cardioversion , total conversion rates in the quinidine and sotalol groups were comparable ( 88 % vs. 68 % , p = 0.17 ) , as was the efficacy of the two drugs in preventing recurrent atrial fibrillation . Side effects necessitating drug discontinuation were more often observed with quinidine . No patient receiving sotalol but four patients receiving quinidine had drug-associated arrhythmia ( torsade de pointes in three patients , sustained ventricular tachycardia in one patient ) . Precordial QT dispersion determined on the surface electrocardiogram ( ECG ) increased with quinidine ( mean + /- SD 34 + /- 9 vs. 44 + /- 16 ms , p = 0.02 ) , indicating enhanced inhomogeneity in ventricular repolarization . There was no change in QT dispersion in patients receiving sotalol ( 36 + /- 18 vs. 40 + /- 17 ms , p = 0.44 ) . CONCLUSIONS Quinidine is more effective than sotalol in terminating atrial fibrillation but is associated with more side effects . The proarrhythmic risk may be related to quinidine 's propensity to increase disparity in ventricular repolarization . This risk warrants careful ECG monitoring during the 1st 4 to 7 days of therapy . Because most proarrhythmic effects occurred shortly after restoration of sinus rhythm , observation should continue > or = 2 to 3 days after sinus rhythm is reestablished Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation .  Because concerns have been raised about their potential proarrhythmic effects , therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety . One hundred thirty-six patients with persistent atrial fibrillation were r and omized to receive propafenone 2 mg/kg over 30 minutes , followed by oral propafenone 150 mg 3 times daily or matching placebo . Nonresponders to intravenous therapy underwent direct-current cardioversion . Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo .  Pharmacologic conversion to sinus rhythm was achieved in 29 % of the patients taking propafenone and in 17 % of patients taking placebo ( p > or = 0.10 ) . Subsequent direct-current cardioversion in nonresponders was equally successful ( 70 % ) in both groups ( p > or = 0.10 ) . The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67 % for the propafenone and 35 % for the placebo group ( p < 0.01 ) . Time to atrial fibrillation relapse was more favorable with propafenone than with placebo ( p < 0.001 ) . The incidence of drug-related side effects was 10 % in the propafenone group and 14 % in the placebo group . Thus , " slow " infusion of propafenone seems to be of limited value for terminating atrial fibrillation . Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm Abstract Objective : To investigate the impact of patients ' preferences for the treatment of atrial fibrillation , by using individualised decision analysis combining probability and utility assessment s into a decision tree . Design : Observational study based on interviews with patients . Setting : Eight general practice s in Avon . Participants : 260 r and omly selected patients aged 70–85 years with atrial fibrillation . Main outcome measures : Patients ' treatment preferences regarding anticoagulation treatment ( warfarin )  after individualised decision analysis ; comparison of these preferences with treatment guidelines on the basis of comorbidity and absolute risk and compared with current prescription . Results : Of 195 eligible patients , 97 participated in decision making using decision analysis . Among these 97 , the decision analysis indicated that 59 ( 61 % ; 95 % confidence interval 50 % to 71 % ) would prefer  anticoagulation treatment — considerably fewer than those who would be recommended treatment according to guidelines . There was marked disagreement between the decision analysis and guideline recommendations ( kappa = 0.25 or less ) . Of 38 patients whose decision analysis indicated a preference for anticoagulation , 17 ( 45 % ) were being prescribed warfarin ; on the other h and , 28 ( 47 % ) of 59 patients were not being prescribed warfarin although the results of their decision analysis suggested they wanted to be . Conclusions : In the context of shared decision making , individualised decision analysis is valuable in a sizeable proportion of elderly patients with atrial fibrillation . Taking account of patients ' preferences would lead to fewer prescriptions for warfarin than under published guideline recommendations . Decision analysis as a shared decision making tool should be evaluated in a r and omised controlled trial 1 . The efficacy of verapamil alone , or in combination with digoxin , was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study . 2 . After 2 weeks on each treatment regimen , heart rate at rest and during progressive load treadmill exercise , left ventricular function at rest and nocturnal heart rate were measured . 3 . Oral verapamil alone at a dose of 80 mg three times daily , or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily , was superior to digoxin alone in doses associated with high serum digoxin concentrations ( mean + /- SEM 1.6 + /- 0.3 micrograms/l ) . This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities , and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia . 4 . We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin OBJECTIVES This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation . BACKGROUND Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events . However , the prognostic implication s of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown . METHOD The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography .  Clinical and echocardiographic data were collected at baseline , and patients were prospect ively followed up , and all strokes , other embolic events and deaths were documented . The relation between spontaneous contrast at baseline and subsequent stroke , other embolic events and survival was analyzed . RESULTS Left atrial spontaneous echo contrast was detected at baseline in 161 patients ( 59 % ) . The mean follow-up was 17.5 months . The stroke or other embolic event rate was 12%/year ( 15 strokes , 3 transient ischemic attacks , 2 peripheral embolisms ) in patients with , compared with 3%/year ( 5 strokes ) in patients without , baseline spontaneous contrast ( p = 0.002 ) . In 149 patients without previous thromboembolism , the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast ( p = 0.003 ) . There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast . Patients with spontaneous contrast had significantly reduced survival ( p = 0.025 ) . On multivariate analysis , spontaneous contrast was the only positive predictor ( odds ratio 3.5 , p = 0.03 ) and warfarin therapy on follow-up the only negative predictor ( odds ratio 0.23 , p = 0.02 ) of subsequent stroke or other embolic events . CONCLUSIONS Transesophageal echocardiography can risk stratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast . These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival , and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable BACKGROUND Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation ( AF ) . However , this treatment carries a risk of bleeding and the need for frequent medical monitoring . We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism . METHODS 1044 patients with AF and with at least one thromboembolic risk factor ( congestive heart failure or left ventricular fractional shortening < or = 25 % , previous thromboembolism , systolic blood pressure of more than 160 mm Hg at study enrollment , or being a woman aged over 75 years ) were r and omly assigned either a combination of low-intensity , fixed-dose warfarin ( international normalised ratio [ INR ] 1.2 - 1.5 for initial dose adjustment ) and aspirin ( 325 mg/day ) or adjusted-dose warfarin ( INR 2.0 - 3.0 ) . Drugs were given open-labelled . FINDINGS The mean INR during follow-up of patients taking combination therapy ( n = 521 ) was 1.3 , compared with 2.4 for those taking adjusted-dose warfarin ( n = 523 ) . During follow-up , 54 % of INRs in patients taking combination therapy were 1.2 - 1.5 and 34 % were less than 1.2 . The trial was stopped after a mean , follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism ( primary events ) in patients given combination therapy ( 7.9 % per year ) was significantly higher than in those given adjusted-dose warfarin ( 1.9 % per year ) at an interim analysis ( p < 0.0001 ) , an absolute reduction of 6.0 % per year ( 95 % Cl 3.4 , 8.6 ) by adjusted-dose warfarin . The annual rates of disabling stroke ( 5.6 % vs 1.7 % , p = 0.0007 ) and of primary event or vascular death ( 11.8 % vs 6.4 % , p = 0.002 ) , were also higher with combination therapy . The rates of major bleeding were similar in both treatment groups . INTERPRETATION Low-intensity , fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism ; adjusted-dose warfarin ( target INR 2.0 - 3.0 ) importantly reduces stroke for high-risk patients In this prospect i ve , controlled and r and omized cross-over study we tried to establish the efficiency and safety of flecainide vs procainamide for the treatment of acute atrial fibrillation .  Eighty patients ( 30 females , 50 males , mean age : 55 + /- 14 years ) were included . Patients entered into the study if they had atrial fibrillation of recent onset ( < 24 h ) with a ventricular rate > 100 beats.min-1 at rest and were < 75 years of age . Exclusion criteria were any sign of heart failure , conduction disturbances , sick sinus syndrome or acute ischaemic events . R and omly 40 patients received flecainide  and 40 procainamide as the first treatment . There were no significant clinical difference between the two groups . Procainamide ws given at a dose of 1 g infused over 30 min , and followed by an infusion of 2 mg.min-1 over 1 h. Flecainide was given at a dose of 1.5 mg.kg-1 over 15 min followed by an infusion of 1.5 mg.kg-1 over 1 h. Drug infusion was continued until maximal dose , intolerance or reversion to sinus rhythm . After 1 h of wash out , patients remaining in atrial fibrillation were started on the second drug . Left atrial size was measured by echo . Serum levels of drug and atrial size did not differ between patients who returned to sinus rhythm and those who remained in atrial fibrillation . Conversion to sinus rhythm was achieved in 37 ( 92 % ) of the 40 patients treated with flecainide and 25 ( 65 % ) of those treated with procainamide ( P < 0.001 ) . The time required for reversion to sinus rhythm was similar between the two groups . ( ABSTRACT TRUNCATED AT 250 WORDS Adjusted-dose warfarin is effective for stroke prevention in patients with nonrheumatic atrial fibrillation ( AF ) , but the risk of bleeding is high , especially among the elderly . Fixed minidose warfarin is effective in preventing venous thromboembolism with low risk of bleeding and no need for frequent clinical monitoring . Patients > 60 years with nonrheumatic AF were r and omized in an open-labeled trial to receive fixed minidose warfarin ( 1.25 mg/day ) or st and ard adjusted-dose warfarin ( International Normalized Ratio [ INR ] between 2.0 and 3.0 ) . Primary outcome events were ischemic stroke , peripheral or visceral embolism , cerebral or fatal bleeding , and vascular death . Secondary end points were major bleeding , myocardial infa rct ion , and death . This study was discontinued before completion in light of publication of the Stroke Prevention in Atrial Fibrillation III trial , which indicated that low-intensity fixed-dose warfarin treatment ( i.e. , INR < 1.5 ) was insufficient for stroke prevention in high-risk patients with nonrheumatic AF . From a total of 1,209 considered patients , 303 were r and omized to be studied ( 150 in the minidose group and 153 in the adjusted-dose group ) . Mean follow-up was 14.5 months . The rate of cumulative primary events was 11.1 % ( 95 % confidence intervals [ CI ] 4.0 to 18.2 ) in the fixed minidose group and 6.1 % ( 95 % CI 1.1 to 11.1 ) in the adjusted-dose group ( p = 0.29 ) . The rate of ischemic stroke was significantly higher in the minidose group ( 3.7 % vs 0 % per year , p = 0.025 ) . Major bleedings were more frequent in st and ard treatment group ( 2.6 % vs 1 % per year , p = 0.19 ) . Most thromboembolic complications occurred at INRs < 1.2 , whereas the majority of hemorrhages occurred at INRs > 3.0 . No significant difference in primary outcome events was observed in the abbreviated study . However , the significantly increased occurrence of ischemic stroke in the fixed minidose warfarin group suggests that this regimen does not protect patients with nonrheumatic AF AIMS The DAAF Trial was design ed to investigate whether digoxin , within 16 h of its use , increases the rate of conversion to sinus rhythm in patients with acute atrial fibrillation . METHODS AND RESULTS In a r and omized , double-blind multicentre trial the effects of intravenous digoxin and placebo , ( mean dose 0.88 + /- 0.35 mg and 0.96 + /- 0.37 mg ) were compared in 239 patients with a mean age of 66.2 + /- 13.0 years and atrial fibrillation of , at most , 7 days ' duration . The mean arrhythmia duration was 21.7 + /- 30.4 h and baseline heart rate 122.0 + /- 23.0 beats.min-1 . At 16 h , 46 % of the placebo group and 51 % of the digoxin group had converted to sinus rhythm , ( ns ) . Time to sinus rhythm was shorter in the digoxin group , but the difference was not significant . Digoxin had a pronounced and rapid effect on heart rate , which was already significant at 2 h ; 104.6 + /- 20.9 beats.min-1 vs 116.8 + /- 22.5 beats.min-1 ( P = 0.0001 ) . CONCLUSION Acute intravenous treatment with digoxin does not increase the rate of conversion to sinus rhythm , but has a fast acting and clinical ly significant effect on heart rate and should remain an alternative in haemodynamically stable patients Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation ( AF ) , there is a clinical need to test newer agents . One hundred patients with AF who had unsuccessful therapy with 1.9 + /- 1.0 type IA antiarrhythmic agents were r and omized to receive either propafenone ( n = 50 ) or sotalol ( n = 50 ) . Patients were stratified into 4 groups based on AF pattern ( chronic vs paroxysmal ) and left atrial size ( large [ > or = 4.5 cm ] vs small [ < 4.5 ] ) . The proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method . For patients r and omized to propafenone , 46 + /- 8 % , 41 + /- 8 % and 30 + /- 8 % remained in sinus rhythm at 3 , 6 and 12 months , respectively , after cardioversion . A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up ( 49 + /- 7 % , 46 + /- 8 % and 37 + /- 8 % at 3 , 6 and 12 months , respectively ; p = NS ) . The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension . Except for constipation that occurred more frequently in patients treated with propafenone , adverse side effects were equally distributed between the 2 therapies . Two patients receiving sotalol died during follow-up . Propafenone and sotalol , 2 new antiarrhythmic agents , were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF . Response rates were not affected by arrhythmia pattern , left atrial size or unsuccessful prior drug therapy . ( ABSTRACT TRUNCATED AT 250 WORDS Transesophageal echocardiography ( TEE ) has emerged as an efficient method for detecting left atrial ( LA ) thrombi in recent years , but its accuracy has not been fully evaluated . A prospect i ve clinicopathologic study in 213 consecutive patients with chronic rheumatic mitral valve disease over a period of 39 months was undertaken . All patients underwent open heart surgery within 3 days after the TEE study . The presence or absence of LA thrombi was confirmed at surgery by direct inspection of the left atrium and proven by histopathologic examination . Of the 213 patients , 147 had predominant mitral stenosis , and the remaining 66 patients had significant mitral regurgitation . Twenty-eight patients had LA thrombi by TEE criteria . These findings were all confirmed at surgicopathologic studies ( specificity 100 % ) . However , in 2 patients , LA thrombi were present but could not be detected by TEE ( sensitivity 93.3 % ) . Therefore , the positive predictive value was 100 % , the negative predictive value was 98.9 % and the diagnostic accuracy was 99.1 % . No thrombi were found in patients with significant mitral regurgitation . The frequency of LA thrombi in patients with predominant mitral stenosis was 20 % ( 30 of 147 ) , and most of these patients had chronic atrial fibrillation ( 28 of 30 , 93 % ) . Only 16 patients ( 16 of 30 , 53 % ) were found to have LA thrombi by transthoracic echocardiography . Furthermore , our data showed poor correlation between the echogenicity of LA thrombi and the degree of thrombus organization . Thus , TEE is excellent for detecting LA thrombi in patients with rheumatic heart disease severe enough to warrant mitral valve operations Objective To compare the efficacy and safety of a single dose of ibutilide , a new class III antiarrhythmic drug , with that of dl-sotalol in terminating chronic atrial fibrillation or flutter in haemodynamically stable patients . Design Double blind , r and omised study . Setting 43 European hospitals . Patients 308 patients ( mean age 60 years , 70 % men , 48 % with heart disease ) with sustained atrial fibrillation ( n = 251 ) or atrial flutter ( n = 57 ) ( duration three hours to 45 days ) were r and omised to three groups to receive a 10 minute infusion of 1 mg ibutilide ( n = 99 ) , 2 mg ibutilide ( n = 106 ) , or 1.5 mg/kg dl-sotalol ( n = 103 ) . Infusion was discontinued at termination of the arrhythmia . Main outcome measure Successful conversion of atrial fibrillation or flutter , defined as termination of arrhythmia within one hour of treatment . Results Both drugs were more effective against atrial flutter than against atrial fibrillation .  Ibutilide was superior to dl-sotalol for treating atrial flutter ( 70 % and 56%v 19 % ) , while the high dose of ibutilide was more effective for treating atrial fibrillation than dl-sotalol ( 44 % v 11 % ) and the lower dose of ibutilide ( 44%v 20 % , p < 0.01 ) . The mean ( SD ) time to arrhythmia termination was 13 ( 7 ) minutes with 2 mg ibutilide , 19 ( 15 ) minutes with 1 mg ibutilide , and 25 ( 17 ) minutes with dl-sotalol . In all patients , the duration of arrhythmia before treatment was a predictor of arrhythmia termination , although this was less obvious in the group that received 2 mg ibutilide . This dose converted almost 48 % of atrial fibrillation that was present for more than 30 days . Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were not predictive of arrhythmia termination . Bradycardia ( 6.5 % ) and hypotension ( 3.7 % ) were more common side effects withdl-sotalol . Of 211 patients given ibutilide  , two ( 0.9 % ) who received the higher dose developed polymorphic ventricular tachycardia , one of whom required direct current cardioversion . Conclusion Ibutilide ( given in 1 or 2 mg doses over 10 minutes ) is highly effective for rapidly terminating persistent atrial fibrillation or atrial flutter . This new class III drug , under monitored conditions , is a potential alternative to currently available cardioversion options This study was performed to evaluate , using a r and omized double-blind , placebo-controlled protocol , the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation ( AF  )  . The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits , the most important being a reduced risk of thromboembolic events .  Three hundred patients with recurrent AF ( > or = 4 episodes in the last year ) and AF at enrollment lasting < 48 hours were r and omized to receive either propafenone ( mean daily dose 13 + /- 1.5 mg/kg ; 102 patients ) , sotalol ( mean daily dose 3 + /- 0.4 mg/kg ; 106 patients ) , or placebo ( 92 patients ) . After 1-year follow-up , Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone ( 63 % ) and sotalol ( 73 % ) and superior to placebo ( 35 % ; p = 0.001 vs both drugs ) . Symptomatic recurrences occurred later with propafenone and sotalol than with placebo . Nine patients ( 9 % ) in the propafenone group , 11 ( 10 % ) in the sotalol group , and 3 ( 3 % ) in the placebo group discontinued therapy due to adverse effects . Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only , and occurred < 72 hours from the beginning of therapy in 4 patients ( 4 % ) . During recurrences , the ventricular rate was significantly reduced in patients taking propafenone and sotalol ( p = 0.001 for both drugs vs placebo ) . The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease . In patients with recurrent symptomatic AF , propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year . Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo Abstract Among 437 patients in whom electrical conversion of atrial arrhythmia was attempted 228 were on long-term anticoagulant therapy and 209 were not given anticoagulants .  Thirteen ( 3 per cent ) had an embolic episode , 2 of the 186 patients in the anticoagulant group and 11 of the 162 patients in the comparative group whose arrhythmias were converted . This difference is statistically significant at the 5 per cent level ( p = 0.012 ) . Three of 11 patients with a history of embolic episodes , whose arrhythmia was converted without anticoagulants , had a new episode after conversion , compared to none of the 55 patients with previous episodes who were receiving anticoagulant therapy . We attach importance to the significant difference in embolic episodes between the two groups even if the patients were not allocated at r and om , perhaps even greater importance , because the difference in composition of the two groups produced a bias against the anticoagulant group . For example , patients with a history of previous embolic episodes and those with rheumatic valvular disease were considerably over-represented in this group . In both of these categories an increased risk of embolism is present . Our results lead to the conclusion that prophylactic anticoagulant therapy is clearly indicated before and after attempts to convert atrial fibrillation in patients with a history of previous embolic episodes . In our opinion such prophylaxis should preferably be given in connection with attempts at conversion in all cases OBJECTIVES The purpose of this study was to assess the effectiveness of azimilide , a class III antiarrhythmic drug , in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation , atrial flutter or both . BACKGROUND Atrial fibrillation is an increasingly common disorder of the heart rhythm , and most patients with this problem are identified because they have symptoms associated with their arrhythmia . New antiarrhythmic therapies are needed to treat patients with this problem . METHODS A total of 384 patients with a history of atrial fibrillation , atrial flutter or both were r and omly assigned to receive once daily doses of placebo or azimilide ; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram ( ECG ) recording . Azimilide 50 mg , 100 mg or 125 mg was tested ; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test . RESULTS In the primary efficacy analysis , the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group ( chi-square 7.96 , p = 0.005 ) ; the hazard ratio ( placebo : azimilide ) for this comparison was 1.58 ( 95 % confidence interval [ CI ] = 1.15 , 2.16 ) . In comparisons between individual doses and placebo , the hazard ratio for the 50 mg daily dose was 1.17 ( 95 % CI = 0.83 , 1.66 ; p = 0.37 ) ; for the 100 mg group , dose was 1.38 ( 95 % CI = 0.96 , 1.98 ; p = 0.08 ) , and for the 125 mg group , dose was 1.83 ( 95 % CI = 1.24 , 2.70 ; p = 0.002 ) . CONCLUSIONS Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation , atrial flutter or both Rapid , reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation . The mainstay of therapy in this arrhythmia has been quinidine . More recently , amiodarone was shown in non-comparative studies to be superior to class IA agents under certain conditions . In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years , the efficacy and safety of either quinidine and verapamil ( days 1 to 3 , quinidine 1,500 mg/day ; days 4 to 6 , quinidine 1,500 mg + verapamil 240 mg/day ) or amiodarone therapy ( days 1 to 3 , amiodarone 1,200 mg/day intravenously ; days 4 to 14 , amiodarone 800 mg/day orally ) were r and omly examined . Responders continued on their effective medication for 3 months . Thereafter , all patients were treated with a fixed regimen of quinidine ( 480 mg/day ) plus verapamil ( 240 mg/day ) for up to 2 years . During atrial fibrillation , quinidine reduced mean ventricular cycle length by 40 ms ( -5 % ) , quinidine and verapamil increased mean cycle length by 57 ms ( 8 % ) and amiodarone by 192 ms ( 28 % , p less than 0.01 ) . In addition , quinidine and verapamil had a characteristic " rate-smoothing " effect on atrioventricular conduction during atrial fibrillation . The rhythm was converted to sinus rhythm after quinidine in 5 ( 25 % ) of 20 patients and after the combination of quinidine and verapamil in 11 ( 55 % ) of 20 patients . Amiodarone restored sinus rhythm in 12 ( 60 % ) of 20 patients . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract In summary , biplane TEE had a high sensitivity and specificity , but a low positive predictive accuracy , for detecting left atrial thrombus in 60 patients who underwent mitral valve surgery . The high falsepositive rate observed in this study appears to reflect the difficulty in differentiating severe spontaneous echo contrast from thrombus on TEE BACKGROUND Currently available antiarrhythmic drugs have limited efficacy for acute termination of atrial fibrillation and flutter , especially if the arrhythmia is not of recent onset . The purpose of this multicenter study was to determine the efficacy and safety of repeated doses of intravenous ibutilide , a class III antiarrhythmic drug , in terminating atrial fibrillation or flutter . METHODS AND RESULTS Two hundred sixty-six patients with sustained atrial fibrillation ( n = 133 ) or flutter ( n = 133 ) , with an arrhythmia duration of 3 hours to 45 days , were r and omized to receive up to two 10-minute infusions , separated by 10 minutes , of ibutilide ( 1.0 and 0.5 mg or 1.0 and 1.0 mg ) or placebo . The conversion rate was 47 % after ibutilide and 2 % after placebo ( P < .0001 ) . The two ibutilide dosing regimens did not differ in conversion efficacy ( 44 % versus 49 % ) . Efficacy was higher in atrial flutter than fibrillation ( 63 % versus 31 % , P < .0001 ) . In atrial fibrillation but not flutter , conversion rates were higher in patients with a shorter arrhythmia duration or a normal left atrial size . Arrhythmia termination occurred a mean of 27 minutes after start of the infusion . Of 180 ibutilide-treated patients , 15 ( 8.3 % ) developed polymorphic ventricular tachycardia during or soon after the infusion . The arrhythmia required cardioversion in 3 patients ( 1.7 % ) and was nonsustained in 12 patients ( 6.7 % ) . CONCLUSIONS Intravenous ibutilide given in repeated doses is effective in rapidly terminating atrial fibrillation and flutter and under monitored conditions is an alternative to current cardioversion options This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation . The study was performed in a r and omized cross-over fashion . Treatment effects were assessed by 24-h ambulatory electrocardiography and symptomatic improvement by symptom scores . The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation . With an attenuation of daytime tachycardia , prevention of nocturnal bradycardia and reduction in the length of nocturnal pauses in rhythm . Overall heart rate variability was significantly less with digoxin and pindolol ( 523 beats min-1 h-1 ) than with digoxin and verapamil ( 745 beats min-1 h-1 ) . We conclude that , in the dosages employed , combined digoxin and pindolol therapy is superior to either digoxin and verapamil in combination or digoxin alone for the treatment of atrial fibrillation 54 patients with chronic atrial fibrillation were r and omly divided into two groups and treated respectively with practolol and quinidine ( 26 cases ) and with placebo and quinidine ( 28 cases ) . Sinus rhythm was restored in about the same percentage of cases in the two groups ( 42.3 and 46.4 % ) . This suggests the following conclusions : practolol is devoid of therapeutic activity in the treatment of chronic atrial fibrillation ; in agreement with similar observations made with other β-adrenergic blocking agents ( propranolol , LB 46 , and alprenolol ) , practolol seems to protect the myocardium from the onset of severe ventricular arrhythmia during the course of quinidine therapy BACKGROUND Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke . We investigated whether anticoagulation with warfarin would reduce this risk . METHODS We conducted a r and omized , double-blind , placebo-controlled study to evaluate low-intensity anticoagulation with warfarin ( prothrombin-time ratio , 1.2 to 1.5 ) in 571 men with chronic nonrheumatic atrial fibrillation ; 525 patients had not previously had a cerebral infa rct ion , whereas 46 patients had previously had such an event . The primary end point was cerebral infa rct ion ; secondary end points were cerebral hemorrhage and death . RESULTS Among the patients with no history of stroke , cerebral infa rct ion occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years ( 4.3 percent per year ) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years ( 0.9 percent per year ) . The reduction in risk with warfarin therapy was 0.79 ( 95 percent confidence interval , 0.52 to 0.90 ; P = 0.001 ) . The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group ( risk reduction , 0.79 ; P = 0.02 ) . The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group . Other major hemorrhages , all gastrointestinal , occurred in 10 patients : 4 in the placebo group , for a rate of 0.9 percent per year , and 6 in the warfarin group , for a rate of 1.3 percent per year . There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group ( risk reduction , 0.31 ; P = 0.19 ) . Cerebral infa rct ion was more common among patients with a history of cerebral infa rct ion ( 9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group ) than among those without such a history . CONCLUSIONS Low-intensity anticoagulation with warfarin prevented cerebral infa rct ion in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage . This benefit extended to patients over 70 years of age
target: They also have an increased risk for thromboembolism .
  Comparing with age-matched controls , the relative risk for stroke is increased 2- to 7-fold in patients with nonrheumatic atrial fibrillation ( 3 , 8 , 13 ) , and the absolute risk for stroke is between 1 % and 5 % per year , depending on clinical characteristics ( 3 , 12 , 14 - 16 ) .
  Paroxysmal atrial fibrillation disrupts the lives of patients ( 17 ) , but this perception may not be associated with frequency or duration of symptoms .
  Warfarin therapy affects quality of life because of frequent blood testing and recommendations for limiting some activities .
  Data Synthesis Does Aggressive Rhythm Control Improve Mortality and Morbidity Compared with Rate Control ?
background: Atrial fibrillation is the most common type of arrhythmia in adults , accounting for about one third of hospitalizations for arrhythmia ( 1 ) .
  The prevalence increases from less than 1 % in persons younger than 60 years of age to more than 8 % in those older than 80 years of age ( 2 - 6 ) .
  The incidence ranges from 0.2 % per year for men 30 to 39 years of age to 2.3 % per year in men 80 to 89 years of age ( 7 , 8) .
  The age-adjusted incidence for women is about half that of men ( 9 ) .
  The cardiac conditions most commonly associated with atrial fibrillation are rheumatic mitral valve disease , coronary artery disease , congestive heart failure , and hypertension ( 8 , 10 ) .
  Noncardiac causes include hyperthyroidism , hypoxic conditions , surgery , and alcohol intoxication .
  A predisposing condition exists in more than 90 % of cases ( 5 , 11 , 12 ) ; the remaining cases have what is called lone atrial fibrillation .
  Patients with atrial fibrillation frequently have symptoms of hemodynamic compromise , ranging from irregular palpitations to the more insidious feeling of malaise .
  Little is known about the direct effects of antiarrhythmic therapy and rate-control therapy on quality of life .
  The American College of Cardiology/American Heart Association/European Society of Cardiology Task Force on Clinical Guidelines for the Management of Atrial Fibrillation classified atrial fibrillation into 4 types ( 20 ) : first detected episode , paroxysmal ( terminates spontaneously ) , persistent ( electrical or pharmacologic termination necessary ) , and permanent ( resistant to electrical or pharmacologic conversion or accepted by the physician ) .
  The purpose of this review was to summarize the evidence that was available during formulation of the guidelines developed by the American College of Physicians ( ACP ) and the American Academy of Family Physicians ( AAFP ) for management of adult patients with nonpostoperative atrial fibrillation .
  Although the relative benefits and risks of rate versus rhythm control are of paramount importance in the management of atrial fibrillation , studies directly addressed this issue only recently .