Antiarrhythmic efficacy of azimilide in patients with atrial fibrillation. Maintenance of sinus rhythm after conversion to sinus rhythm. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. Comparative effects of carvedilol and amiodarone on conversion and recurrence rates of persistent atrial fibrillation. Efficacy and proarrhythmic hazards of pharmacologic cardioversion of atrial fibrillation: prospective comparison of sotalol versus quinidine. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: implications for optimal patient care. A Randomized, Placebo-Controlled Study of Vernakalant (Oral) for the Prevention of Atrial Fibrillation Recurrence After Cardioversion Intravenous amiodarone versus verapamil for acute conversion of paroxysmal atrial fibrillation to sinus rhythm. Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Amiodarone versus sotalol for atrial fibrillation. The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation. Maintenance of sinus rhythm in patients with atrial fibrillation: an AFFIRM substudy of the first antiarrhythmic drug. Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators. Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm; a randomized study. Natural History and Long-Term Outcomes of Ablated Atrial Fibrillation Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department Amiodarone, sotalol, or propafenone in atrial fibrillation: which is preferred to maintain normal sinus rhythm? Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Ibutilide versus amiodarone in atrial fibrillation: A double-blinded, randomized study A randomized trial of circumferential pulmonary vein ablation versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation: the APAF Study. Management of Newly Detected Atrial Fibrillation: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians Comparison of oral loading dose of propafenone and amiodarone for converting recent-onset atrial fibrillation. PARSIFAL Study Group. An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation. Clinical course of recent-onset atrial fibrillation treated with oral propafenone. Ablation for longstanding permanent atrial fibrillation: results from a randomized study comparing three different strategies. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. Radiofrequency Catheter Ablation and Antiarrhythmic Drug Therapy: A Prospective, Randomized, 4-Year Follow-Up Trial: The APAF Study Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. Effects of Amiodarone and Diltiazem on Persistent Atrial Fibrillation Conversion and Recurrence Rates: A Randomized Controlled Study [Sotalol and quinidine/verapamil (Cordichin) in chronic atrial fibrillation--conversion and 12-month follow-up--a randomized comparison]. Sotalol versus propafenone for long-term maintenance of normal sinus rhythm in patients with recurrent symptomatic atrial fibrillation. Treatment of atrial fibrillation and paroxysmal supraventricular tachycardia with bidisomide. The Atrial Fibrillation Investigation with Bidisomide (AFIB) Investigators. Oral Propafenone To Convert Recent-Onset Atrial Fibrillation in Patients with and without Underlying Heart Disease A comparison of rate control and rhythm control in patients with atrial fibrillation. Efficacy of three different ablative procedures to treat atrial fibrillation in patients with valvular heart disease: a randomised trial. Results of a Minimally Invasive Surgical Pulmonary Vein Isolation and Ganglionic Plexi Ablation for Atrial Fibrillation: Single-Center Experience With 12-Month Follow-Up
BACKGROUND Azimilide dihydrochloride ( azimilide ) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias . In patients with atrial fibrillation , it has shown excellent efficacy in some previous trials and minimal efficacy in others . METHODS Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter , r and omized , placebo-controlled clinical trial . Patients were admitted to a hospital and r and omly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily . Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital .  Recurrence of atrial fibrillation was documented by electrocardiogram . In the primary efficacy analysis , time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease . Safety was assessed as deaths , adverse events , and serious adverse events . RESULTS A total of 446 patients were r and omized in the study ; 314 were in the subgroup with structural heart disease . The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days , and the difference between treatments was not significant ( P = .4596 , n = 314 ) . The relative risk for recurrence ( placebo : azimilide ) was 1.104 ( 95 % CI 0.849 - 1.436 ) . There was 1 death in the placebo group and 3 in the azimilide group . CONCLUSIONS Azimilide did not demonstrate clinical ly important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to 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 We conducted a r and omized , controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation . METHODS A total of 146 patients with a mean ( + /-SD ) age of 57+/-9 years who had chronic atrial fibrillation were r and omly assigned to receive amiodarone and undergo two cardioversions during the first three months alone ( the control group ) or in combination with circumferential pulmonary-vein ablation . Cardiac rhythm was assessed with daily telephonic transmissions for one year . The left atrial diameter and the severity of symptoms were assessed at 12 months . RESULTS Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation , ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent . An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year ( P=0.05 ) . Among the 69 patients in the control group , 53 ( 77 percent ) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 ( 4 percent ) were in sinus rhythm without antiarrhythmic-drug therapy or ablation . There were significant decreases in the left atrial diameter ( 12+/-11 percent , P<0.001 ) and the symptom severity score ( 59+/-21 percent , P<0.001 ) among patients who remained in sinus rhythm after circumferential pulmonary-vein ablation . Except for atypical atrial flutter , there were no complications attributable to circumferential pulmonary-vein ablation . CONCLUSIONS Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy , cardioversion , or both . The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter Pretreatment with antiarrhythmic agents could improve cardioversion and recurrence rates in patients with persistent atrial fibrillation . In a prospect i ve controlled trial , 145 patients were r and omly assigned to treatment with carvedilol , amiodarone , or placebo for 4 weeks before electrical cardioversion . Although the 2 drugs had similar effects on cardioversion rates , amiodarone was superior in terms of sinus rhythm maintenance after conversion 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 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 ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on OBJECTIVES The present study determined the incidence and time course of atrial fibrillation ( AF ) recurrences  in patients with a history of AF and fitted with an implantable monitoring device .  BACKGROUND The long-term risk of undetected recurrence of AF in patients receiving stable antiarrhythmic therapy remains uncertain . METHODS In 110 patients with a class I indication for physiologic pacing and a history of AF , a pacemaker with dedicated functions for AF detection and electrogram storage was implanted , and antiarrhythmic drug treatment was optimized . Patients were regularly followed up with evaluation of AF-related symptoms , a  resting electrocardiogram ( ECG ) , and  interrogation of device memory .  The incidence of AF recurrences lasting > 48 h in asymptomatic patients presenting in sinus rhythm ( SR ) at the respective follow-up visit constituted the primary end point of this prospect i ve study . RESULTS During 19 + /- 11 months , 678 follow-up visits were performed . Atrial fibrillation was documented in 51 patients ( 46 % ) by ECG recording and in 97 patients ( 88 % ) by a review of stored electrograms ( p < 0.0001 ) . Device interrogation revealed AF recurrences lasting > 48 h in 50 patients , 19 of whom ( 38 % ) were completely asymptomatic and in SR at subsequent follow-up . In 11 ( 16 % ) of 67 patients with device-confirmed freedom from AF for > or =3 months , AF lasting > 48 h recurred subsequently . CONCLUSIONS This prospect i ve study demonstrates a high incidence of recurrent AF despite optimized antiarrhythmic therapy . Of particular note , AF relapses > 48 h remained totally asymptomatic in a significant proportion of patients . Freedom from AF for > or =3 months did not preclude subsequent long-lasting AF recurrence Background — Vernakalant , a relatively atrial-selective antiarrhythmic drug , has previously demonstrated efficacy for the acute conversion of atrial fibrillation ( AF ) to sinus rhythm . This study was design ed to determine the most appropriate oral dose of vernakalant for the prevention of AF recurrence postcardioversion . Methods and Results — Patients with nonpermanent AF were r and omized to 150 , 300 , or 500 mg vernakalant or placebo twice daily for up to 90 days . The efficacy analysis was conducted on 605 of 735 patients who entered the maintenance phase on day 3 after cardioversion . The time to the first recurrence of symptomatic sustained AF was significantly longer in the 500 mg vernakalant group , with a median of > 90 days versus 29 days in the placebo group ( hazard ratio , 0.735 ; P=0.0275 ) . No significant effect was seen at the lower doses . The percent of patients in sinus rhythm at day 90 was 41 % , 39 % , and 49 % in the 150-mg ( n=147 ) , 300-mg ( n=148 ) , and 500-mg ( n=150 ) vernakalant groups , respectively , compared with 36 % in the placebo group ( n=160 ) . There were no vernakalant-related proarrhythmic events . Related serious adverse events occurred in 2 patients in the 150-mg vernakalant group and in 1 patient in each of the other groups . Conclusions — Vernakalant , 500 mg twice daily , appears to be effective and safe for the prevention of AF recurrence after cardioversion . The absence of proarrhythmia and favorable safety profile is an important finding for the drug . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00526136 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 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 BACKGROUND Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization . Sinus rhythm may be maintained with antiarrhythmic drugs , but some of these drugs increase the risk of death . METHODS We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals . We r and omly assigned 762 patients to receive dofetilide , a novel class III antiarrhythmic agent , and 756 to receive placebo in a double-blind study . Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment . The primary end point was death from any cause . RESULTS During a median follow-up of 18 months , 311 patients in the dofetilide group ( 41 percent ) and 317 patients in the placebo group ( 42 percent ) died ( hazard ratio , 0.95 ; 95 percent confidence interval , 0.81 to 1.11 ) . Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure ( risk ratio , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ) . Dofetilide was effective in converting atrial fibrillation to sinus rhythm . After one month , 22 of 190 patients with atrial fibrillation at base line ( 12 percent ) had sinus rhythm restored with dofetilide , as compared with only 3 of 201 patients ( 1 percent ) given placebo . Once sinus rhythm was restored , dofetilide was significantly more effective than placebo in maintaining sinus rhythm ( hazard ratio for the recurrence of atrial fibrillation , 0.35 ; 95 percent confidence interval , 0.22 to 0.57 ; P<0.001 ) . There were 25 cases of torsade de pointes in the dofetilide group ( 3.3 percent ) as compared with none in the placebo group . CONCLUSIONS In patients with congestive heart failure and reduced left ventricular function , dofetilide was effective in converting atrial fibrillation , preventing its recurrence , and reducing the risk of hospitalization for worsening heart failure .  Dofetilide had no effect on mortality BACKGROUND AND OBJECTIVES The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined . This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study , a r and omized clinical trial comparing warfarin , aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation . METHODS Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents . The relative risk of cardiac mortality , including arrhythmic death , in patients receiving antiarrhythmic drug therapy  was determined and adjusted for other cardiac risk factors . RESULTS In patients receiving antiarrhythmic drug therapy , cardiac mortality was increased 2.5-fold ( p = 0.006 , 95 % confidence interval [ CI ] 1.3 to 4.9 ) and arrhythmic death was increased 2.6-fold ( p = 0.02 , 95 % CI 1.2 to 5.6 ) . Among patients with a history of congestive heart failure , those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 ( p less than 0.001 , 95 % CI 1.9 to 11.6 ) compared with that of patients not so treated ; the relative risk of arrhythmic death in the treated group was 3.7 ( p = 0.01 , 95 % CI 1.3 to 10.4 ) . Patients without a history of congestive heart failure had no increased risk of cardiac mortality ( relative risk 0.70 , 95 % CI 0.2 to 3.1 ) during antiarrhythmic drug therapy . After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death , patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death . However , in patients with a history of heart failure who received antiarrhythmic drug therapy , the relative risk of cardiac death was 3.3 ( p = 0.05 , 95 % CI 0.99 to 11.1 ) and that of arrhythmic death was 5.8 ( p = 0.009 , 95 % CI 1.5 to 21.7 ) compared with the risk in patients not taking antiarrhythmic medications . CONCLUSIONS Although antiarrhythmic drug therapy was not r and omly determined in this trial , the data suggest that in patients with atrial fibrillation and a history of congestive heart failure , the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm BACKGROUND The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone ( 267 patients ) , sotalol ( 261 patients ) , or placebo ( 137 patients ) and monitored them for 1 to 4.5 years . The primary end point was the time to recurrence of atrial fibrillation beginning on day 28 , determined by means of weekly transtelephonic monitoring . RESULTS Spontaneous conversion occurred in 27.1 percent of the amiodarone group , 24.2 percent of the sotalol group , and 0.8 percent of the placebo group , and direct-current cardioversion failed in 27.7 percent , 26.5 percent , and 32.1 percent , respectively . The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group , 74 days in the sotalol group , and 6 days in the placebo group according to intention to treat and 809 , 209 , and 13 days , respectively , according to treatment received . Amiodarone was superior to sotalol ( P<0.001 ) and to placebo ( P<0.001 ) , and sotalol was superior to placebo ( P<0.001 ) . In patients with ischemic heart disease , the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy ( P=0.53 ) . Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity . There were no significant differences in major adverse events among the three groups . CONCLUSIONS Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm .  Amiodarone is superior for maintaining sinus rhythm , but both drugs have similar efficacy in patients with ischemic heart disease . Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance 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 OBJECTIVES This study sought to determine whether ablation of complex fractionated atrial electrograms ( CFAEs ) after antral pulmonary vein isolation ( APVI ) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation ( AF ) . BACKGROUND Ablation of CFAEs has been reported to eliminate persistent AF . However , residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence . METHODS In this r and omized study , 119 consecutive patients ( mean age 60 + /- 9 years ) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter . Antral pulmonary vein isolation result ed in termination of AF in 19 of 119 patients ( Group A , 16 % ) . The remaining 100 patients who still were in AF were r and omized to no further ablation and underwent cardioversion ( Group B , n = 50 ) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration ( Group C , n = 50 ) . RESULTS Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients ( 18 % ) in Group C. At 10 + /- 3 months after a single ablation procedure , 18 of 50 ( 36 % ) in Group B and 17 of 50 ( 34 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.84 ) . In Group A , 15 of 19 patients ( 79 % ) were in sinus rhythm . A repeat ablation procedure was performed in 34 of 100 r and omized patients ( for AF in 30 and atrial flutter in 4 ) . At 9 + /- 4 months after the final procedure , 34 of 50 ( 68 % ) in Group B and 30 of 50 ( 60 % ) in Group C were in sinus rhythm without antiarrhythmic drugs ( p = 0.40 ) . CONCLUSIONS Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF OBJECTIVES This study evaluated the efficacy of antiarrhythmic drugs for the treatment of  atrial fibrillation ( AF ) .  BACKGROUND The most effective and safest antiarrhythmic drug for the treatment of AF is unknown . METHODS The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study compared two treatment strategies -- rate control and rhythm control -- in patients with AF and risk factors for stroke or death . This sub study , performed in patients r and omized to rhythm control , compared different antiarrhythmic drugs by r and omly assigning the first drug treatment to : 1 ) amiodarone , 2 ) sotalol , or 3 ) a class I drug . The primary end point was the proportion of patients alive , in sinus rhythm , with no additional cardioversions and still taking the assigned drug at one year . Comparisons were made between patients eligible for each of three drug pairs . RESULTS At one year , in 222 patients r and omized between amiodarone and class I agents , 62 % were successfully treated with amiodarone , compared with 23 % taking class I agents ( p < 0.001 ) . In 256 patients r and omized between amiodarone and sotalol , 60 % versus 38 % were successfully treated , respectively ( p = 0.002 ) . In 183 patients r and omized between sotalol and class I agents , 34 % versus 23 % were successfully treated , respectively ( p = 0.488 ) , although this portion of the sub study was stopped early when amiodarone was shown to be better than class I agents . Sinus rhythm was achieved in nearly 80 % of patients at one-year follow-up with serial therapy . Adverse effects were common . CONCLUSIONS Amiodarone was more effective at one year than either sotalol or class I agents for the strategy of maintenance of sinus rhythm without cardioversion 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 AIMS The aim of this prospect i ve , r and omized study was to determine the efficacy of a serial external electrical cardioversion strategy in maintaining sinus rhythm after 12 months in patients with recurrent persistent atrial fibrillation . METHODS AND RESULTS Ninety patients with persistent atrial fibrillation lasting more than 72 h but less than 1 year were r and omized in a one to one fashion to repetition of up to two electrical cardioversions in the event of relapse of atrial fibrillation detected within 1 month of the previous electrical cardioversion ( Group AGG ) , or to non-treatment of atrial fibrillation relapse ( Group CTL ) .  ECGs  were scheduled at 6 h , 7 days , and 1 month .  Clinical examination and ECGs  were repeated during the 6-month and 12-month follow-up examinations .  Echocardiography  was repeated during the 6-month follow-up examination . Clinical and echocardiographic characteristics were similar in the two groups . All patients were treated with antiarrhythmic drugs before electrical cardioversion and throughout follow-up . After 12 months , sinus rhythm was maintained in 53 % of Group AGG patients and in 29 % of Group CTL patients ( P<0.03 ) . After 6 months , left ventricular ejection fraction had recovered significantly only in Group AGG ( 56.8 + /- 9.0 % at enrollment vs 60.4 + /- 9.4 % at 6 months , P < 0.001 ) . CONCLUSION These results demonstrate that an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm after 12 months Background —Atrial  fibrillation ( AF ) ablation  is increasingly used in clinical practice . We aim ed to study the natural history and long-term outcomes of ablated AF . Methods and Results —We followed 831 patients after pulmonary vein isolation ( PVI ) performed in 2005 . We documented clinical outcomes using our prospect i ve AF registry with most recent up date on this group of patients in October 2009 . In the first year after ablation , 23.8 % had early recurrence . Over long-term follow-up ( 55 months ) , only 8.9 % had late arrhythmia recurrence defined as occurring beyond the first year after ablation . Repeat ablations in patients with late recurrence revealed conduction recovery in at least 1 of the previously isolated PVs in all of them and right-sided triggers with isoproterenol testing in 55.6 % . At last follow-up , clinical improvement was 89.9 % ( 79.4 % arrhythmia-free off antiarrhythmic drugs and 10.5 % with AF controlled with antiarrhythmic drugs ) . Only 4.6 % continued to have drug-resistant AF . It was possible to safely discontinue anticoagulation in a substantial proportion of patients with no recurrence in the year after ablation ( CHADS score ⩽2 , stroke incidence of 0.06 % per year ) . The procedure-related complication rate was very low . Conclusions —Pulmonary vein isolation is safe and efficacious for long-term maintenance of sinus rhythm and control of symptoms in patients with drug-resistant AF . It obviates the need for antiarrhythmic drugs , negative dromotropic agents , and anticoagulants in a substantial proportion of patients Aims Ibutilide is a rapid‐acting antiarrhythmic drug with worldwide use for conversion of recent‐onset atrial fibrillation . Vernakalant , approved in the EU in 2010 , is likewise used intravenously , with proven efficacy and safety compared with placebo and amiodarone in r and omized clinical trials . The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent‐onset atrial fibrillation treated with vernakalant or ibutilide .  Methods and results A r and omized controlled trial registered at clinical trials.gov ( NCT01447862 ) was performed in 100 patients with recent‐onset atrial fibrillation treated at the emergency department of a tertiary care hospital . Patients received up to two short infusions of vernakalant ( n = 49 ; 3 mg/kg followed by 2 mg/kg if necessary ) or ibutilide ( n = 51 ; 1 mg followed by another 1 mg if necessary ) according to the manufacturer 's instructions . Clinical and laboratory variables , adverse events , conversion rates , and time to conversion were recorded . Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group ( median time : 10 vs. 26 min , P = 0.01 ) , and likewise the conversion success within 90 min was significantly higher in the vernakalant group ( 69 vs. 43 % , log‐rank P = 0.002 ) . No serious adverse events occurred . Conclusion Vernakalant was superior to ibutilide in converting recent‐onset atrial fibrillation to sinus rhythm in the emergency department setting 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 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 Objective Ibutilide , a class III antiarrhythmic drug , has been shown to convert atrial fibrillation to sinus rhythm more rapidly than procainamide or sotalol . Our objective was to compare the efficacy and safety of ibutilide and amiodarone in patients after cardiac surgery . Design Prospect i ve , r and omized , double-blinded study . Setting Intensive care unit of a university hospital . Patients Forty adults with an onset of atrial fibrillation within 3 hrs after admission . Interventions Before the administration of antiarrhythmic drugs , a 24-hr Holter electrocardiograph was attached . Patients in the ibutilide group received ibutilide 0.008 mg/kg body weight over 10 mins ; treatment was repeated if atrial fibrillation or flutter persisted . If sinus rhythm was not achieved within 4 hrs , amiodarone 5 mg/kg was administered over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs . Patients in the amiodarone group received amiodarone 5 mg/kg over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs if atrial fibrillation or flutter continued . Measurements and Main Results Within the first 4 hrs , atrial fibrillation was converted in nine of 20 patients ( 45 % ) in group ibutilide and in ten of 20 patients ( 50 % ) in group amiodarone ( not significant ) . Mean time for conversion overall was 385 mins in group ibutilide and 495 mins in group amiodarone ( not significant ) . In group amiodarone , the protocol was discontinued in two patients because of severe arterial hypotension . Atrial fibrillation recurred in 11 of 20 patients ( 55 % ) in group ibutilide and in seven of 20 patients ( 35 % ) in group amiodarone ( not significant ) . Ventricular arrhythmia did not occur during the first 24 hrs of the protocol . Conclusions Ibutilide has no significant advantage over amiodarone for the conversion of atrial fibrillation to sinus rhythm in either time to conversion or conversion overall , but severe hypotension was not seen with ibutilide OBJECTIVES We compared ablation strategy with antiarrhythmic drug therapy ( ADT ) in patients with paroxysmal atrial fibrillation ( PAF ) . BACKGROUND Atrial fibrillation ( AF ) ablation strategy is superior to ADT in patients with an initial history of PAF , but its role in patients with a long history of AF as compared with ADT remains a challenge . METHODS One hundred ninety-eight patients ( age , 56 + /- 10 years ) with PAF of 6 + /- 5 years ' duration ( mean AF episodes 3.4/month ) who had failed ADT were r and omized to AF ablation by circumferential pulmonary vein ablation ( CPVA ) or to the maximum tolerable doses of another ADT , which included flecainide , sotalol , and amiodarone . Crossover to CPVA was allowed after 3 months of ADT . RESULTS By Kaplan-Meier analysis , 86 % of patients in the CPVA group and 22 % of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias ( AT ) ( p < 0.001 ) ; a repeat ablation was performed in 9 % of patients in the CPVA group for recurrent AF ( 6 % ) or atrial tachycardia ( 3 % ) . At 1 year , 93 % and 35 % of the CPVA and ADT groups , respectively , were AT-free . Ejection fraction , hypertension , and age independently predicted AF recurrences in the ADT group . Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations ( p < 0.01 ) . One transient ischemic attack and 1 pericardial effusion occurred in the CPVA group ; side effects of ADT were observed in 23 patients . CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications . Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired . ( A Controlled R and omized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF : APAF/01 ; http:// clinical trials.gov/ct/show ; NCT00340314 ) Atrial fibrillation is the most common type of arrhythmia in adults . It is more common as patients age ; the prevalence is 1 % among those younger than age 60 years and increases to more than 8 % in those older than age 80 years . When data are adjusted for age , men are affected more often than women . Cardiac conditions associated with the development of atrial fibrillation are hypertension , rheumatic mitral valve disease , coronary artery disease , and congestive heart failure . Noncardiac causes include hyperthyroidism , hypoxic pulmonary conditions , surgery , and alcohol intoxication . Patients with atrial fibrillation may have symptoms of hemodynamic compromise , such as irregular palpitations and lightheadedness , or more vague symptoms , such as malaise , but may be asymptomatic . Patients with atrial fibrillation are at increased risk for thromboembolic disease . The purpose of this guideline is to make recommendations on the pharmacologic management of newly detected atrial fibrillation in primary care . The target patient population is adult patients with first-detected atrial fibrillation , defined as the presence of symptoms or electrocardiographic evidence of atrial fibrillation . The American College of Cardiology/American Heart Association has recommended using first-detected atrial fibrillation regardless of whether it is symptomatic or self-limited , recognizing that there can be uncertainty about the duration of the episode and about previous undetected episodes ( 1 ) . This guideline does not apply to patients with postoperative or postmyocardial infa rct ion atrial fibrillation , patients with class IV heart failure , patients already taking antiarrhythmic drugs , or patients with valvular disease . The target physician audience is internists and family physicians dedicated to primary care . This guideline is based on the accompanying background paper by McNamara and colleagues ( 2 ) and on the evidence report Management of New-Onset Atrial Fibrillation ( 3 ) , which was produced by the Johns Hopkins Evidence -based Practice Center under contract to the Agency for Healthcare Research and Quality ( AHRQ ) , Rockville , Maryl and . The American Academy of Family Physicians ( AAFP ) and the American College of Physicians ( ACP ) created this guideline in collaboration . The Joint AAFP/ACP Panel review ed the evidence and developed and grade d the recommendations ( Table 1 ) . The guideline was then approved by both organizations . The guideline makes recommendations in the following areas : rate control versus rhythm control , stroke prevention and anticoagulation , electrical cardioversion versus pharmacologic cardioversion , the role of transesophageal echocardiography in guiding therapy , and maintenance therapy . Table 1 . The Guyatt Approach to Grading Recommendations * Section 1 : Rate Control versus Rhythm Control One of the fundamental questions in the management of atrial fibrillation is whether to attempt cardioversion . The answer to this question depends on whether rate control or rhythm control provides more effective protection from thromboembolic events , improved mortality , better relief of symptoms , or improved quality of life . Another significant clinical question is whether certain population s , such as women , patients with hypertension or congestive heart failure , or young people with structurally healthy hearts , have better outcomes with one or the other strategy . Four studies have compared rate control with rhythm control . The study sample s have generally involved older patients ( > 65 years of age ) , and women and younger patients with healthy hearts and paroxysmal atrial fibrillation have not been well represented ( 5 ) . The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) trial compared rhythm control versus rate control , and use of anticoagulation was recommended in both arms ( 6 ) . More than 4000 patients who were at least 65 years of age or who had at least 1 risk factor for stroke or death , such as hypertension , diabetes , previous stroke , or poor ventricular function , were followed for a mean of 3.5 years . Slightly more than one third of the patients were enrolled after their first episode of atrial fibrillation , and more than 90 % had had their qualifying episode within the previous 6 weeks . In more than two thirds of patients , the qualifying episode lasted at least 2 days . The average patient age was 70 years . Sixty-one percent of patients were men , and 89 % were white . Seventy-one percent of patients had hypertension , 38 % had coronary heart disease , 18 % had previously had failure of antiarrhythmic therapy , and 12 % had no apparent heart disease ( lone atrial fibrillation ) . Patients were r and omly assigned to rate or rhythm control , and their physicians chose the specific therapies ( pharmacologic first , then nonpharmacologic if needed ) . Anticoagulation was continued indefinitely in the rate-control group and was encouraged in the rhythm-control group but could be stopped at the physician 's discretion if sinus rhythm had been maintained for at least 4 , and preferably 12 , consecutive weeks with antiarrhythmic therapy . The prevalence of sinus rhythm in the rhythm-control group was 82 % , 73 % , and 63 % at 1 , 3 , and 5 years , respectively . The prevalence of sinus rhythm in the rate-control group was 34.6 % at 5 years . The primary end point in the AFFIRM trial , overall mortality , was not statistically significantly different between the groups . However , the rhythm-control strategy was associated with a higher risk for death than the rate-control strategy among older patients , those without congestive heart failure , and those with coronary disease .  Rates of stroke also did not differ between groups ; 70 % of all strokes occurred in patients who had stopped receiving anticoagulation or who had subtherapeutic international normalized ratios ( < 2.0 ) . More hospitalizations were reported in the rhythm-control group ( P < 0.001 ) . Another recent study , the RAte Control versus Electrical cardioversion for persistent atrial fibrillation ( RACE ) study , r and omly assigned patients to receive aggressive rhythm control or rate control ( 7 ) . This was a smaller study , involving 522 patients ( mean age , 68 years ) . Sixty-four percent of patients were men , 49 % had hypertension , and 27 % had coronary artery disease . All patients had persistent atrial fibrillation lasting less than 1 year and had had at least 1 previous electrical cardioversion ( a maximum of 2 previous cardioversions was permitted for study inclusion ) . The primary end point was a composite of cardiovascular mortality , heart failure , thromboembolic complications , bleeding , pacemaker implantation , and severe side effects of antiarrhythmic drugs . Again , no difference was seen between groups in the primary composite end point . As in the AFFIRM study , most of the strokes occurred in patients whose anticoagulation had been halted or patients whose international normalized ratio was subtherapeutic ( < 2.0 ) . In post hoc analysis , a benefit for rate control over rhythm control was seen in patients with hypertension and in women . Since this was a post hoc analysis , these results will need to be confirmed by further studies . Of note , despite an aggressive treatment protocol , at the end of follow-up only 39 % of the patients in the rhythm-control group were in sinus rhythm . The Pharmacological Intervention in Atrial Fibrillation ( PIAF ) trial r and omly assigned 252 patients 18 to 75 years of age with new-onset or permanent symptomatic atrial fibrillation ( mean duration of atrial fibrillation , approximately 4 months ) to rate control with diltiazem or aggressive conversion ( many times if necessary ) and maintenance therapy with amiodarone ( 8) . The primary end point of the study was improvement in symptoms related to atrial fibrillation . After 1 year of follow-up , relief of symptoms was similar in both groups , as were quality -of-life measures . Walking distance was improved in the rhythm-control group , but hospital admissions were more frequent in this group . Although final results are not yet available , preliminary reports of the Strategies of Treatment of Atrial Fibrillation ( STAF ) trial have been presented ( 9 ) . Patients were r and omly assigned to receive anticoagulation for 3 weeks before conversion and for 4 weeks after attempted conversion , with antiarrhythmic therapy to maintain sinus rhythm , or to long-term anticoagulation and rate control . ( Patients included in this study had at least 1 previous conversion attempt . ) After more than 1.5 years of follow-up , no difference was seen between the groups in rates of the primary end points of death , stroke , transient ischemic attacks , cardiopulmonary resuscitation , or thromboembolism . Of interest , only 40 % of patients in the rhythm-control group were still in sinus rhythm at 1 year , and all primary end points occurred in patients in atrial fibrillation , even in the rhythm-control group . This result has created speculation about whether fewer events would have occurred if anticoagulation had been continued indefinitely in the conversion group . It also suggests that despite aggressive rhythm management , a substantial number of patients can not maintain sinus rhythm . In general , the trial sample s were older and male and had risk factors for stroke , such as hypertension , congestive heart failure , and coronary disease . Certain subgroups of patients with atrial fibrillation , such as younger patients with healthy hearts or paroxysmal atrial fibrillation , were not well represented in the trials . Therefore , it is not certain whether these subgroups of patients may benefit from more aggressive rhythm control or rate control . Recommendation 1 : Rate control with chronic anticoagulation is the recommended strategy for the majority of patients with atrial fibrillation . Rhythm control has not been shown to be superior to rate control ( with chronic anticoagulation ) in reducing morbidity and mortality and may be inferior in some patient subgroups to rate control . Rhythm 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 AIMS Permanent atrial fibrillation develops in many patients after ablation and pacing therapy .  We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm . METHODS AND RESULTS In this multicentre r and omized controlled trial , 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned , after successful atrioventricular junction ablation and pacing treatment  , to antiarrhythmic drug therapy with amiodarone , propafenone , flecainide or sotalol and were compared with 69 patients assigned , after successful AV junction ablation and pacing treatment , to no antiarrhythmic drug therapy . The patients were followed-up for 12 to 24 months ( mean 16+/-4 ) . The drug arm patients had a 57 % reduction in the risk of developing permanent atrial fibrillation ( 21 % vs 37 % , P=0.02 ) . Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups , but the drug arm patients had more episodes of heart failure and hospitalizations ( P=0.05 ) . The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not . CONCLUSION Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy . The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing 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 BACKGROUND This prospect i ve multicenter r and omized study aim ed to compare the efficacy of 3 common ablation methods used for longst and ing permanent atrial fibrillation ( AF ) . METHODS A total of 144 patients with longst and ing permanent AF ( median duration 28 months ) were r and omly assigned to circumferential pulmonary vein ablation ( CPVA , group 1 , n = 47 ) , to pulmonary vein antrum isolation ( PVAI , group 2 , n = 48 ) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms ( CFAE ) in both atria followed by a pulmonary vein antrum isolation ( CFAE + PVAI , group 3 , n = 49 ) . RESULTS Scarring in the left atrium and structural heart disease/hypertension were present in most patients ( 65 % ) . After a mean follow-up of 16 months , 11 % of patients in group 1 , 40 % of patients in group 2 and 61 % of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs ( P < .001 ) . Sinus rhythm maintenance would increase respectively to 28 % ( group 1 ) , 83 % ( group 2 ) , and 94 % ( group 3 ) after 2 procedures and with antiarrhythmic drugs ( AADs , P < .001 ) . The AF terminated during ablation , either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia , in 13 % of patients ( group 1 ) , 44 % ( group 2 ) , and 74 % ( group 3 ) respectively . CFAE alone , performed as the first step of the ablation in group 3 , organized AF in only 1 patient . CONCLUSION In this study , the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longst and ing permanent AF . Electrical isolation of the PVs , although inadequate if performed alone , is relevant to achieve long-term sinus rhythm maintenance after ablation . Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation 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 Background — Information on comparative outcome between radiofrequency catheter ablation ( RFA ) and antiarrhythmic drugs ( AADs ) > 1 year after r and omization is important for clinical decision-making . Methods and Results — A total of 198 patients ( age , 56±10 years ) with paroxysmal atrial fibrillation were r and omly assigned to RFA ( 99 patients ) or to AADs ( 99 patients ) . We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis . Cardiac rhythm was assessed with daily transtelephonic transmissions . Quality of life was also analyzed . At 4 years , among the 99 patients first assigned to RFA , the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients ( 27.3 % ) . Among the 99 patients r and omly assigned to AADs , 87 ( 87.9 % ) crossed over to undergo RFA and 4 years after r and om assignment only 12 ( 12.1 % ) were in sinus rhythm with AAD alone without ablation . Despite the high level of crossovers , at 4 years the intention-to-treat analysis showed that 72.7 % of patients in the ablation arm and 56.5 % of those initially r and omly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia ( P=0.017 ) . During the follow-up , 19.2 % of AAD patients progressed to persistent atrial fibrillation before switching to RFA . RFA significantly improved quality of life ( P<0.001 ) , whereas before crossing over to RFA , patients receiving AADs showed poorer quality of life . Except for new left atrial tachycardia , there were no serious complications caused by RFA . Conclusions — With follow-up extended to 4 years after r and omly assigned , ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00340314 OBJECTIVES This study was design ed to compare two treatment strategies in patients with atrial fibrillation(AF ) :  rhythm-control ( restoration and maintenance of sinus rhythm ) and rate-control ( pharmacologic or invasive rate-control and anticoagulation ) . BACKGROUND Atrial fibrillation is the most common arrhythmia . It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality , morbidity , and quality of life . METHODS The Strategies of Treatment of Atrial Fibrillation ( STAF ) multicenter pilot trial r and omized 200 patients ( 100 per group ) with persistent AF to rhythm- or rate-control .  The combined primary end point was a combination of death , cardiopulmonary resuscitation , cerebrovascular event , and systemic embolism . RESULTS After 19.6 + /- 8.9 months ( range 0 to 36 months ) there was no difference in the primary end point between rhythm-control ( 9/100 ; 5.54%/year ) and rate-control ( 10/100 ; 6.09%/year ; p = 0.99 ) . The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period ( rate-control group ) was 23 % ( 0 % ) at 36 months . Eighteen primary end points occurred in atrial fibrillation ; only one occurred in sinus rhythm ( p = 0.049 ) . CONCLUSIONS The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations . These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence . It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients , as all but one end point occurred during AF Abstract Purpose : To assess the effects of amiodarone and diltiazem on atrial fibrillation ( AF ) induced atrial electrical remodeling and their clinical implication s. Methods : Persistent AF patients were r and omly assigned to three treatment groups over a period from 6 weeks before to 6 weeks after internal cardioversion : group A ( 35 patients , oral diltiazem ) , group B ( 34 patients , oral amiodarone ) and group C ( 37 patients , no antiarrhythmic drugs ) . Several electrophysiological parameters were assessed 5 min and 24 h after cardioversion . Results : Compared with controls , group B patients had significantly higher conversion rates ( 83 % vs. 100 % , p = 0.041 ) and a higher probability to maintain sinus rhythm ( p = 0.037 ) . Patients of group B had longer fibrillatory cycle length intervals than patients of group A and C ( 180 ± 18 ms vs. 161 ± 17 ms vs. 164 ± 19 ms , p = 0.001 ) and longer atrial effective refractory periods ( 211 ± 22 ms vs. 198 ± 16 ms vs. 194 ± 17 ms , p = 0.003 ) as assessed 5 min after conversion . Post-conversion density of supraventricular ectopics was significantly lower in group B compared to groups A and C ( p = 0.001 ) . Conclusions : Oral amiodarone  increases conversion rates , prolongs fibrillatory cycle length and atrial effective refractory period and preserves sinus rhythm after cardioversion in persistent AF patients by suppressing the atrial ectopics that trigger AF Atrial fibrillation is one of the most common arrhythmias , leading at least in a subset of patients to severe symptoms ( palpitations , weakness , syncope ) , and to hemodynamic impairment especially in the clinical setting of left ventricular dysfunction . Thus , in many cases restauration of sinus rhythm is indicated because of the negative effects of reduced cardiac output .  Quinidine has been the first line drug for many years and has been proven to be highly effective especially when combined with Verapamil . But there is growing concern about using quinidine and other class I-anti-arrhythmic agents because of some hints in clinical trials for increased longterm mortality on these drugs . This study was undertaken to test the efficacy of Sotalol , a beta-blocker with additional strong class-III antiarrhythmic action , compared to a fixed combination of Quinidine and Verapamil for conversion of chronic atrial fibrillation and maintenance of sinus rhythm after medical or electrical cardioversion . To avoid early proarrhythmic effects , potassium values in the range of " high"-normal values ( > 4.3 mval/L ) were tried to be obtained . 82 patients were r and omly assigned to receive either  Sotalol or Quinidine/Verapamil . There was no difference between the groups as far as the underlying heart disease , duration of atrial fibrillation ( mean 219 days ) and other clinical features including echocardiographic parameters were concerned . The dose of the drug was weight-related individually adjusted , and the drug was continued thereafter . If sinus rhythm could not be established at that time , electric cardioversion was performed and the drug was continued in lower dosage thereafter . ( ABSTRACT TRUNCATED AT 250 WORDS This prospect i ve , r and omized , single-blinded , placebo-controlled study compared the efficacy and safety of sotalol and propafenone when used for long-term prevention of  atrial fibrillation .  For the long-term maintenance of normal sinus rhythm , propafenone seems to be more effective than sotalol BACKGROUND Atrial fibrillation and paroxysmal supraventricular tachycardia are common disorders of the heart rhythm for which antiarrhythmic drug therapy is commonly prescribed . The Atrial Fibrillation Investigation with Bidisomide ( AFIB ) study was a r and omized , placebo-controlled clinical trial design ed to accomplish three goals in a single protocol : ( 1 ) to determine the efficacy of the antiarrhythmic drug bidisomide in the treatment of these two arrhythmias ; ( 2 ) to establish the appropriate dose range for bidisomide ; and ( 3 ) to detect an adverse mortality effect of bidisomide if one were present in patients with atrial fibrillation . METHODS AND RESULTS In this clinical trial , 1227 patients with atrial fibrillation and 187 with paroxysmal supraventricular tachycardia were r and omly assigned to bidisomide ( 200 , 400 , or 600 mg BID ) or placebo ; patient groups with each arrhythmia were analyzed separately . Symptomatic recurrences of atrial fibrillation and paroxysmal supraventricular tachycardia were documented with the use of transtelephonic ECG monitoring . The time to the first symptomatic arrhythmia recurrence was measured in each patient and compared among treatment groups . Among the atrial fibrillation patients , there was no significant difference in the time to first symptomatic recurrence between the placebo group and any of the three bidisomide treatment groups ; the hazard ratios ( placebo : treatment ) were 1.19 , 1.03 , and 1.14 for bidisomide 200 , 400 , and 600 mg BID , respectively . Among paroxysmal supraventricular tachycardia patients , there was a similar lack of a significant treatment effect ; the hazard ratios were 1.30 , 1.93 , and 1.59 for bidisomide 200 , 400 , and 600 mg BID , respectively . In the primary safety analysis of mortality , 3 of 493 patients taking placebo  died , compared with 9 of 488 patients taking one of the two higher doses of bidisomide ( P>.10 ) . CONCLUSIONS Bidisomide in the doses tested did not have a clinical ly important antiarrhythmic effect . The AFIB study provided a novel clinical trial design to test antiarrhythmic drugs for both safety and efficacy 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 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 OBJECTIVES Various modifications have been proposed to the original Cox 's Maze procedure due to concerns about the long bypass and cross clamp times . The efficacy of these procedures has been studied and reported . We conducted a r and omised prospect i ve study to compare three procedures , differing in extent , of ablation in patients in atrial fibrillation who were undergoing surgery for rheumatic valvular heart disease . These procedures utilised radiofrequency in the bipolar mode . The extent of ablation was ( 1 ) biatrial ( replication of the Cox Maze ) ( 2 ) left atrial portion of the Cox Maze and ( 3 ) pulmonary vein isolation along with a control group ( the No Maze group ) . Conversion rate to sinus rhythm was studied over a mid-term follow-up period . METHODS A total of 160 patients were studied with 40 patients in each group .  Antiarrhythmic drugs were not used in the three months preceding surgery and for seven days postoperatively . The patients underwent surgery for their valve disease along with the ablative procedure as per r and omisation using radiofrequency microbipolar coagulation and cryoablation . They were followed up and were evaluated for symptomatic improvement , rhythm with ECG documentation and 2D echocardiography . RESULTS Follow-up was available for 133 patients . Mid-term results showed that sinus rhythm was restored in 62.5 % patients of Biatrial Maze group and 57.5 % in the Left Atrial Maze . In the Pulmonary Vein Isolation Maze group , 67.5 % patients converted to NSR whereas in the No Maze group only 20 % patients were in sinus rhythm ( p value for all the groups was 0.001 when compared to the No Maze group ) . The incidence of other arrhythmias was not significant and there were no other major complications . All the patients in sinus rhythm at follow-up were in NYHA functional class I-II and showed good effort tolerance . CONCLUSIONS Results achieved with the three ablative procedures are comparable . Therefore lesser procedures viz . Left Atrial Maze and the Pulmonary Vein Isolation Maze procedures must be studied further with the additional use of antiarrhythmic drugs Background —The Cox Maze procedure for treatment of medically refractory atrial fibrillation ( AF ) is limited by its complexity and requirement for cardiopulmonary bypass . Long-term follow-up and success using criteria established by the Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society consensus statement have not been reported for surgical AF ablation . We describe the results of using a thorascopic approach and radiofrequency energy to perform bilateral pulmonary vein isolation and left atrial ganglionic plexi ablation for treatment of AF . Methods and Results —Forty-five ( 33 paroxysmal ; 12 persistent ) consecutive patients underwent thorascopic bilateral radiofrequency pulmonary vein isolation , ganglionic plexi ablation , ligament of Marshall ablation , and left atrial appendage exclusion by a single surgeon . Forty-three patients were prospect ively followed without antiarrhythmic drugs for a minimum of 1 year with a 30-day continuous event monitor or pacemaker interrogation at 6 and 12 months . Failure was defined as any atrial tachyarrhythmia of > 30 seconds ’ duration occurring > 90 days after surgery . Mean follow-up was 516±181 days ( 202 to 858 days ) . Twenty-eight ( 65 % ) patients had no atrial tachyarrhythmia > 30 seconds by 1 year , and 15 ( 35 % ) patients had atrial tachyarrhythmia recurrences by 1 year . Eight of 15 patients with recurrent AF had catheter ablation result ing in elimination and /or reduction of AF episodes in 7 of 8 patients . Four of 15 patients had AF elimination or reduction with antiarrhythmic drugs alone . Three patients did not benefit from surgery and received rate control only . There were no deaths ; 1 phrenic nerve injury and 2 pleural effusions were the only major complications . Conclusions —The single procedure success at 1-year follow-up for surgical pulmonary vein isolation and ganglionic plexi ablation is 65 % . Atrial tachyarrhythmia recurrences after surgery are usually responsive to catheter ablation and /or antiarrhythmic drugs
No other antiarrhythmic showed a significant effect on mortality compared with controls .
Class IA , IC , and III drugs are effective in maintaining sinus rhythm but increase adverse effects , and class IA drugs may increase mortality
BACKGROUND A variety of antiarrhythmic drugs have been used to prevent recurrence of atrial fibrillation after conversion to sinus rhythm .
We performed a systematic review to determine the effect of long-term treatment with those drugs on death , embolisms , adverse effects , and atrial fibrillation recurrence .