A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation. The effect of ranolazine on maintaining sinus rhythm in patients with resistant atrial fibrillation Risk of proarrhythmic events in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: a multivariate analysis. 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. Atrial fibrillation postcardiac surgery: a common but a morbid complication. Digoxin for converting recent-onset atrial fibrillation to sinus rhythm. A randomized, double-blinded trial. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation. A double-blind study comparing quinidine, disopyramide and placebo. Cardiac rate normalization in chronic atrial fibrillation: comparison of long-term efficacy of treatment with amiodarone versus AV node ablation and permanent His-bundle pacing. [Sotalol and quinidine/verapamil (Cordichin) in chronic atrial fibrillation--conversion and 12-month follow-up--a randomized comparison]. Management of Newly Detected Atrial Fibrillation: A Clinical Practice Guideline from the American Academy of Family Physicians and the American College of Physicians Efficacy and late recurrences with wide electrical pulmonary vein isolation for persistent and permanent atrial fibrillation. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. Propafenone versus sotalol for suppression of recurrent symptomatic atrial fibrillation. Atrial fibrillation in patients with heart failure: Role of catheter ablation therapies. Long-term follow-up of direct current cardioversion after cardiac surgery with special reference to quinidine1 Efficacy and Safety of Oral Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic Atrial Fibrillation or Atrial Flutter: The Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) Study Conversion efficacy of intravenous ibutilide compared with intravenous amiodarone in patients with recent-onset atrial fibrillation and atrial flutter. Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators. Functional status in rate- versus rhythm-control strategies for atrial fibrillation: results of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Functional Status Substudy. Atrial fibrillation: an observational study with outpatients. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. Outpatient treatment of recent-onset atrial fibrillation with the "pill-in-the-pocket" approach. Propafenone versus disopyramide for maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: A randomized, double-blind study
OBJECTIVES The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating  recent onset atrial fibrillation ( AF ) .  BACKGROUND Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety . RSD1235 is a novel atrial selective anti-arrhythmic drug . METHODS This was a phase II , multi-centered , r and omized , double-blinded , step-dose , placebo-controlled , parallel group study . Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were r and omized to one of two  RSD1235  dose groups or to placebo . The two RSD1235 groups were RSD-1 ( 0.5 mg/kg followed by 1 mg/kg ) or RSD-2 ( 2 mg/kg followed by 3 mg/kg ) , by intravenous infusion over 10 min ; a second dose was given only if AF was present . The primary end point was termination of AF during infusion or within 30-min after the last infusion . Secondary end points included the number of patients in sinus rhythm at 0.5 , 1 , and 24 h post-last infusion and time to conversion to sinus rhythm . RESULTS The RSD-2 dose showed significant differences over placebo in : 1 ) termination of AF ( 61 % vs. 5 % , p < 0.0005 ) ; 2 ) patients in sinus rhythm at 30 min ( 56 % vs. 5 % , p < 0.001 ) ; 3 ) sinus rhythm at 1 h ( 53 % vs. 5 % , p = 0.0014 ) ; and 4 ) median time to conversion to SR ( 14 vs. 162 min , p = 0.016 ) . There were no serious adverse events related to RSD1235 . CONCLUSIONS RSD1235 , a new atrial-selective anti-arrhythmic agent , appears to be efficacious and safe for converting recent onset AF to sinus rhythm Background Atrial fibrillation ( AF ) may arise out of anomalous impulse activity at atrial venous junctions . Triggered activity may be a source of abnormal impulse activity . Ranolazine is an anti-anginal agent , which inhibits normal and abnormal late Na+ channel current in the ventricle and peak Na+ channel current in the atrium . This produces an energy sparing effect and stabilizes cardiac membranes . Ranolazine is a potent inhibitor of triggered activity . The purpose of this report is to describe our initial experience with ranolazine used in patients with resistant AF . Methods Seven patients ( 4 males , 3 females , 67 ± 9 years ) who developed recurrent AF within hours to a few days of restoring sinus rhythm despite AF ablation and /or failing one or more anti-arrhythmic agents  were started on ranolazine ( 500 - 1000 mg/twice/day ) after stopping all other anti-arrhythmic therapy .  All but one patient had some form of associated structural heart disease . Results Two patients received no apparent benefit from ranolazine  developing recurrent AF within 2 days . All other patients derived significant benefit . Four patients have experienced no recurrent AF . The other patient relapsed at 3 months and again at 6 months . The mean time in sinus rhythm to date , or to the first relapse , for the five responders was 27 ± 11 weeks . No clinical ly evident pro-arrhythmic episodes occurred . Conclusion Ranolazine was helpful in maintaining sinus rhythm in the majority of patients in which more established measures had failed . A controlled prospect i ve trial is warranted to further investigate the efficacy of ranolazine in AF OBJECTIVES This study examined the risk of proarrhythmic events in patients receiving antiarrhythmic drugs for treatment of atrial fibrillation ( AF ) according to present-day safety guidelines . BACKGROUND Advances in underst and ing the proarrhythmic risk of antiarrhythmic drugs has led to development of safety guidelines for these agents . Such guidelines were used in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . METHODS This study was an analysis of the risk of arrhythmic events ( arrhythmic death , resuscitated cardiac arrest , sustained ventricular tachycardia ( VT ) , and torsade de pointes VT ) in the antiarrhythmic drug arm of the AFFIRM study . Each time an antiarrhythmic drug was begun , it was counted as an exposure to that drug and the risk of an arrhythmic event was calculated . RESULTS A total of 2,033 patients received 3,030 exposures to antiarrhythmic drugs . Ninety-six arrhythmic events occurred by six years . Patients with a left ventricular ejection fraction < 40 % had more arrhythmic events . Twelve documented cases of torsade de pointes VT were noted . The incidence of torsade de pointes was 0.6 % at five years ( 95 % confidence interval 0.32 to 1.07 ) . CONCLUSIONS The overall risk of adverse arrhythmic events upon exposure to antiarrhythmic drugs in the AFFIRM study was reasonably low . Strict criteria for the safe use of antiarrhythmic drugs were successful in minimizing proarrhythmic events 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 Despite all the advances in cardiac surgery , atrial fibrillation ( AF ) remains a common postoperative complication with unclear predisposing factors . Postoperative AF is often a short-lived and a self-limiting condition , but can result in debilitating and even lethal consequences . The aim of this study is to assess the effect of AF on patients postcardiac surgery . METHODS In this retrospective study , we prospect ively review ed patient data for our institution for a 10-year period ; a total of 17,379 patients with preoperative sinus rhythm ( SR ) who underwent cardiac surgery were included , of which 4984 ( 28.7 % ) had developed postoperative AF for any length of time . After propensity matching for the preoperative characteristics between the two groups ; the group with AF and the group who remained in SR , postoperative complications , in-hospital mortality , mid-term survival rate ( five years ) , and long-term survival rate ( 10 years ) were compared . RESULTS Before and after adjusting for the preoperative characteristics and type of the operation , postoperative complications , such as renal failure , surgical wound infection , stroke and myocardial infa rct ion were significantly higher in the AF group compared to the SR group ( P < 0.001 ) . Inotropic support , use of intra-aortic balloon pump , and ventilation time were also considerably higher in the AF patients ( P < 0.001 ) . In-hospital mortality was also higher in the AF group . Likewise , 30-day , mid-term and long-term mortality rates were found to be considerably higher in the AF group . CONCLUSIONS Despite all the modern anti-arrhythmic drugs , the incidence of AF remains unchanged . Patients who develop AF postcardiac surgery show a significantly worse outcome compared to those without AF . This study also highlights the importance of anticoagulation in AF to prevent the devastating consequences as a result of a cerebral stroke . We believe that not only immediate treatment of AF postoperatively should be implemented , but also measures should be taken to identify the risk factors of AF and to prevent AF postcardiac surgery STUDY OBJECTIVE to determine whether digoxin is effective in converting atrial fibrillation of recent onset to normal sinus rhythm . DESIGN r and omized , double-blinded , placebo-controlled trial with a maximum 18-hour treatment period . SETTING emergency room and medical floors of a non-referral city hospital . PATIENTS consecutive sample of 36 patients with atrial fibrillation of 7 days ' duration or less , not on digitalis glycoside or anti-arrhythmic agents , with ventricular rate between 85 to 175 beats/min , without evidence of heart failure , acute myocardial infa rct ion , unstable angina , preexcitation syndrome , thyrotoxicosis , hypokalemia , renal impairment , or severe metabolic disturbances . INTERVENTIONS digoxin solution in capsules or identical placebo , given in doses of 0.6 , 0.4 , 0.2 , and 0.2 mg , at 0 , 4 , 8 , and 14 hours , respectively , or until conversion to sinus rhythm , whichever occurred first . Continuous electrocardiographic recording by Holter monitor .  MEASUREMENTS AND MAIN RESULTS nine of eighteen patients receiving digoxin  and 8 of 18 receiving  placebo  had a return to sinus rhythm within 18 hours of study entry ( 95 % confidence interval for the difference in proportions , -11 % to 22 % ) . Mean time to conversion was 5.1 hours in the digoxin group and 3.3 in the placebo group ( 95 % Cl , -3.6 to 7.0 hours ) . CONCLUSIONS spontaneous reversion to sinus rhythm is common in patients with atrial fibrillation of recent onset . Digitalization was not shown to affect the likelihood of reversion to sinus rhythm , and thus can not be recommended for this purpose in patients with atrial fibrillation In order to compare the relative efficacy of quinidine , disopyramide and a placebo in the maintenance of sinus rhythm after cardioversion from atrial fibrillation and in order to examine the incidence of side-effects , 82 patients with continuous atrial fibrillation ( duration more than 1 month but less than 3 years ) were r and omized in a double-blind fashion to receive quinidine , disopyramide or placebo . Six months after cardioversion there was no significant difference between any of the three groups as regards the number of patients remaining in sinus rhythm . The greater distortion of the atrial architecture which occurs in patients with rheumatic mitral valve disease may explain the failure of these anti-arrhythmic agents to prolong the duration of sinus rhythm in this study , in which patients with valvular heart disease comprised 76 % of the total group Chronic atrial fibrillation ( AF ) is a common arrhythmia with significant morbidity and mortality . AF has been the subject of considerable attention and intensive clinical research in recent years . Current opinion on the management of AF favors the restoration and maintenance of normal ventricular rhythm . This has several potential benefits , including the alleviation of arrhythmia-associated symptoms and hemodynamic improvements . Maintenance of frequents normalization of ventricular rhythm ( NVR ) can be achieved with antiarrhythmic drug therapy or with AV node radiofrequency ablation ( RFA ) and permanent ventricular pacing . Recent interest has focused on the use of class III antiarrhythmic agents , such as amiodarone hydrochloride . This investigation compared amiodarone to AV node RFA and permanent pacing of the His-bundle area in maintaining NVR in patients with resistant chronic AF . After 12 months of treatment with amiodarone ( 200 to 400 mg/d ) 30 % of patients remained in NVR , 30 % were in transitional phase of improvement , and 40 % showed negative effect . Only a few patients in this group developed ocular or hepatic side effects . On one year follow-up was achieved in 100 % of cases without any clinical ly significant side effects being seen . In conclusion , analysis of the results of this study suggests that low-dose amiodarone is well tolerated in the management of chronic AF in a selected patient population . The more aggressive interventional radiofrequency ablation technique is significantly more effective and more reliable in the long-term clinical treatment of drug-resistant 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 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 AIMS Early recurrences of atrial arrhythmia after wide electrically isolating ablation for atrial fibrillation ( AF ) are well described , but the long-term risk of recurrence for patients with persistent and permanent AF has not been studied in detail . METHODS AND RESULTS Fifty-six consecutive patients [ 45 men ( 80.4 % ) , age 55.9 + /- 8.7 years ] with persistent [ 39(69.6 % ) ] or permanent [ 17(30.4 % ) ] AF were followed for 21.6 + /- 8.8 months after ablation . Atrial fibrillation duration prior to ablation was 6.4 + /- 5.6 years .  Electrically isolating lesions encircling the left and right pulmonary veins ( PVs ) in pairs were created . After 1.5 + /- 0.7 procedures , 48 ( 85.7 % ) had sinus rhythm ( SR ) at 21.6 + /- 8.8 months of follow-up : achieved with 1 procedure in 27 ( 56.3 % ) and without anti-arrhythmics in 30 ( 62.5 % ) . Atrial fibrillation recurrence was observed in 69.6 % after the first and 46.4 % after the last procedure . Of those with late recurrences ( > 90 days ) following the last procedure , most [ 18 ( 69.2 % ) ] did not have early recurrences . Pre-procedural AF duration ( P = 0.007 ) and female gender ( P = 0.005 ) were independent predictors of recurrence following the last procedure . CONCLUSION Circumferential PV isolation is effective in most patients with persistent or permanent AF . However , repeat procedures are frequently required . Late recurrences are common and not precluded by the absence of early post-procedural arrhythmias 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 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 Atrial fibrillation ( AF ) represents the most common sustained cardiac arrhythmia in patients with heart failure ( HF ) . AF in HF patients is associated with worsening of symptoms and also results in a substantial increase in mortality . Although HF patients in sinus rhythm have a better outcome than patients with AF , several r and omized studies investigating pharmacological rhythm control versus rate control have shown no advantage of one strategy over the other in terms of patient outcomes . Catheter-based ablation therapy is a newer therapeutic option with a rapidly evolving and changing role in the management of this arrhythmia . In the present review , the authors discuss the epidemiology , pathophysiology and prognostic significance of AF in patients with HF . Exclusively addressed are studies investigating catheter-based ablation for rhythm-control and rate-control therapies in the management of AF in HF patients The results of the long-term follow-up of 119 patients who had DC cardioversion performed are described . All patients had had corrective cardiac surgery for chronic rheumatic valvar heart disease . The poor prognosis for maintenance of sinus rhythm in this type of patient is emphasized . Of the total patients , 83 per cent were converted to sinus rhythm , but relapses were common in those who had atrial fibrillation before operation . Only 40 per cent of such patients maintained sinus rhythm for 2 months , 15 per cent for 1 year , and 9 per cent for 2 years . By contrast , when atrial fibrillation occurred for the first time in the post-operative period , 82 per cent maintained sinus rhythm for 2 years after conversion . Post-operative DC cardioversion is in general not recommended for patients with rheumatic heart disease and atrial fibrillation unless atrial fibrillation occurs for the first time in the post-operative period . A controlled trial of prophylactic quinidine is reported and shows no significant increase in the number of patients remaining in sinus rhythm as compared with a control group not receiving quinidine Background This double-blind , multicenter , placebo-controlled study determined the efficacy and safety of dofetilide in converting  atrial fibrillation ( AF ) or atrial flutter ( AFl )  to  sinus rhythm ( SR ) and maintaining SR for 1 year . Methods and Results Patients with AF or AFl ( n=325 ) were r and omized to 125 , 250 , or 500 & mgr;g dofetilide or placebo twice daily . Dosages were adjusted for QTc response and , after 105 patients were enrolled , for calculated creatinine clearance ( ClCr ) . Pharmacological cardioversion rates for 125 , 250 , and 500 & mgr;g dofetilide were 6.1 % , 9.8 % , and 29.9 % , respectively , versus 1.2 % for placebo ( 250 and 500 & mgr;g versus placebo;P = 0.015 and P < 0.001 , respectively ) . Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91 % in 36 hours . For the 250 patients who successfully cardioverted pharmacologically or electrically , the probability of remaining in SR at 1 year was 0.40 , 0.37 , 0.58 for 125 , 250 , and 500 & mgr;g dofetilide , respectively , and 0.25 for placebo ( 500 & mgr;g versus placebo , P = 0.001 ) . Two cases of torsade de pointes occurred , 1 on day 2 and the other on day 3 ( 0.8 % of all patients given active drug ) ; 1 sudden cardiac death , classified as proarrhythmic , occurred on day 8 ( 0.4 % of all patients given active drug ) . Conclusions Dofetilide , a new class III antiarrhythmic agent , is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year . In-hospital initiation and dosage adjustment based on QTc and ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk AIM The aim of our study was to compare the efficacy and safety of ibutilide and amiodarone ( intravenously ) in converting  recent-onset atrial fibrillation ( AF ) and atrial flutter ( Af )  to sinus rhythm ( SR ) . METHODS The study was prospect i ve , r and omized and included 152 ( 103 men and 49 women ) consecutive patients with AF or Af of 3 - 48 h duration .  Ibutilide is a selective class III antiarrhythmic agent which when administered intravenously can terminate AF and Af .  Amiodarone is also a class III antiarrhythmic agent that when given intravenously or orally has proved to be more effective than other agents in terminating AF and Af [ B.N. Singh , F.V. Mody , B. Lopez , J.S. Sarma . Antiarrhythmic agents for atrial fibrillation : focus on prolonging atrial repolarization . Am J Cardiol 1999 Nov 4 ; 84 : 161R-173R . ] . Seventy-nine patients ( 56 with AF and 23 with Af ) that consisted group A were treated with ibutilide .  Seventy-three ( 52 with AF and 21 with Af ) consisted group B and were treated with intravenous infusion of amiodarone . RESULTS The conversion rate of group A ( ibutilide ) was significantly higher than the conversion rate of group B ( amiodarone ) ( 80 % vs. 57 % , p=0.0054 ) . As regards the kind of arrhythmia separately , for AF there was n't significant difference ( 77 % vs. 69 % , p = ns ) whereas for Af ibutilide was superior to amiodarone ( 87 % vs. 29 % , p=0.003 ) . The conversion rates of ibutilide did n't differ for AF and Af ( 77 % vs. 87 % , p = ns ) . CONCLUSIONS Ibutilide is more effective than amiodarone in converting recent-onset Af to SR whereas both drugs are equally effective in converting recent-onset AF to SR OBJECTIVES This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide , a pure class III antiarrhythmic agent , for the termination of sustained atrial fibrillation or flutter . BACKGROUND Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation . These effects , and preliminary clinical data , suggest that it may be effective in the treatment of atrial fibrillation and flutter . METHODS Ninety-one patients with sustained atrial fibrillation ( 75 patients ) or flutter ( 16 patients ) were entered into a double-blind , r and omized multicenter study of one of two doses of dofetilide ( 4 or 8 micrograms/kg body weight ) or placebo . RESULTS Dofetilide  effectively terminated the arrhythmia in 31 % of patients receiving 8 micrograms/kg , a statistically significant difference from those receiving 4 micrograms/kg ( conversion rate 12.5 % , p < 0.05 ) or placebo ( no conversion , p < 0.01 ) . Patients with atrial flutter had a greater response to dofetilide ( 54 % conversion rate ) than those with atrial fibrillation ( 14.5 % conversion rate , p < 0.001 ) . CONCLUSIONS Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm . However , its efficacy is greater in flutter -- a response that contrasts with the poorer response seen with class I agents . This finding potentially represents an important advance in the pharmacologic termination of atrial flutter OBJECTIVES The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) functional status sub study aim ed to test the hypothesis that functional status is similar in rate-control and rhythm-control strategies . BACKGROUND R and omized studies , including the AFFIRM study , have failed to demonstrate survival benefits between rate-control and rhythm-control strategies for atrial fibrillation ( AF ) . However , AF may cause functional capacity or cognitive impairment that might justify maintenance of sinus rhythm . METHODS Investigators of the AFFIRM study enrolled 4,060 patients with AF who required long-term therapy and who were 65 years of age or older or who had another risk factor for stroke or death . New York Heart Association functional class ( NYHA-FC ) and Canadian Cardiovascular Society Angina Classification were assessed at initial and each follow-up visit . From 22 r and omly chosen functional status sub study sites , 245 participants underwent  6-min walk tests and Mini-Mental State Examination ( MMSE ) at initial , two-month , and yearly visits . Patients were assigned r and omly to rate-controlling drugs , allowing AF to persist , or rhythm-controlling antiarrhythmic drugs , to maintain sinus rhythm . RESULTS The NYHA-FC worsened with time in both rate-control and rhythm-control groups , with no differences between groups . Presence of AF was associated with worse NYHA-FC ( p < 0.0001 ) . No differences were observed in Canadian Cardiovascular Society Angina Classification or MMSE scores . Six-minute walk distance improved over time in both study arms . On average , walk distance was 94 feet greater in the rhythm-control group ( adjusted p = 0.049 ) . CONCLUSIONS Modest improvement in 6-min walk distance was noted in the rhythm-control arm . Presence of AF was associated with worse NYHA-FC . No difference in cognitive function was detected BACKGROUND Atrial fibrillation ( AF ) is the most common sustained arrhythmia with serious clinical consequences in the absence of treatment . However , there are limited data on the treatment of these patients in Argentina . The objective was to describe the therapeutic management of patients with nonacute AF by Argentinean cardiologists and to determine the incidence of clinical events after 12 months follow-up . METHODS The Atrial Fibrillation study in Argentina ( FARAON ) was an observational , descriptive , prospect i ve , national , and multicentric study that included out patients with AF , followed for 12 months . The study included 38 sites in Argentina . Each research er included the first 10 patients who met the inclusion criteria of being over 21 and also being an AF carrier documented by electrocardiogram or Holter within 12 months prior to or at the time of enrollment . RESULTS A total of 373 patients were included , mean age 70 ± 11.5 years , 40 % women ; 65 % had AF rhythm at the time of inclusion , 57 % had permanent AF , and 56 % were asymptomatic . At the time of enrollment , 40 % of physicians opted for rhythm control strategy . β-blockers and amiodarone were the most used drugs . Patients with rhythm control drugs had higher success rate than those with frequency control drug therapy ( 80 % vs 57 % ) . CONCLUSION Cardiologists in Argentina receive patients with AF that are mostly permanent AF . More than half of the patients are asymptomatic . They opt primarily by controlling the pace . When choosing antiarrhythmic drugs , nearly half of them indicated amiodarone 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 BACKGROUND In-hospital administration of flecainide and propafenone in a single oral loading dose has been shown to be effective and superior to placebo in terminating atrial fibrillation . We evaluated the feasibility and the safety of self-administered oral loading of flecainide and propafenone in terminating atrial fibrillation of recent onset outside the hospital . METHODS We administered either flecainide or propafenone orally to restore sinus rhythm in 268 patients with mild heart disease or none who came to the emergency room with atrial fibrillation of recent onset that was hemodynamically well tolerated . Of these patients , 58 ( 22 percent ) were excluded from the study because of treatment failure or side effects . Out-of-hospital self-administration of flecainide or propafenone -- the " pill-in-the-pocket " approach -- after the onset of heart palpitations was evaluated in the remaining 210 patients ( mean age [ + /-SD ] , 59+/-11 years ) . RESULTS During a mean follow-up of 15+/-5 months , 165 patients ( 79 percent ) had a total of 618 episodes of arrhythmia ; of those episodes , 569 ( 92 percent ) were treated 36+/-93 minutes after the onset of symptoms . Treatment was successful in 534 episodes ( 94 percent ) ; the time to resolution of symptoms was 113+/-84 minutes . Among the 165 patients with recurrences , the drug was effective during all the arrhythmic episodes in 139 patients ( 84 percent ) . Adverse effects were reported during one or more arrhythmic episodes by 12 patients ( 7 percent ) , including atrial flutter at a rapid ventricular rate in 1 patient and noncardiac side effects in 11 patients . The numbers of monthly visits to the emergency room and hospitalizations were significantly lower during follow-up than during the year before the target episode ( P<0.001 for both comparisons ) . CONCLUSIONS In a selected , risk-stratified population of patients with recurrent atrial fibrillation , pill-in-the-pocket treatment is feasible and safe , with a high rate of compliance by patients , a low rate of adverse events , and a marked reduction in emergency room visits and hospital admissions Summary Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic altrial fibrillation ( median arrhythmia duration , 5 months ) . After cardioversion , patients were r and omly assigned to receive double-blind propafenone 300 mg tid ( 25 patients ) or disopyramide 250 mg tid ( 31 patients ) . Downward dose adjustment was allowed in case of intolerable side effects . The endpoints were arrhythmia recurrence ; and side effects not amenable to dose reduction . For patients r and omized to propafenone ( mean dose , 878±65 mg/day ) , 66 % [ 95 % confidence interval [ ( CI ) 46–85 % ] and 55 % ( 95 % CI , 34–76 % ) remained in sinus rhythm at 3 and 6 months , respectively ( Kaplan-Meier method ) . Similar figures were found with disopyramide ( mean dose , 704±81 mg/day ) : 71 % ( 95 % CI , 54–87 % ) and 67 % ( 95 % CI , 50–84 % ) at 3 and 6 months , respectively ( p = NS ) . In the patients with a relapse of atrial fibrillation , the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion . However , one patient on disopyramide had an excessively high relapse heart rate ( 170 vs. 100 beats/min ) . Side effects were more frequent on disopyramide . Side effects necessitating drug discontinuation occurred in 12 patients : 4 patients ( 16 % ) on propafenone and 8 ( 26 % ) on disopyramide  . Severe adverse effects occurred in two patients , who developed heart failure while on disopyramide . There were no proarrhythmic events or deaths . Thus , propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation . Propafenone is , however , better tolerated  than disopyramide , which may cause heart failure
Moreover all the anti-arrhythmic agents that are used in treatment of AF were potentially pro-arrhythmic especially in patients with coronary artery disease and structurally abnormal heart .
Although atrial fibrillation ( AF ) is the most common sustained arrhythmia seen during daily cardiovascular physician practice , its management remained a challenge for cardiology physician as there was no single anti-arrhythmic agents proved to be effective in converting atrial fibrillation and kept its effectiveness in maintaining sinus rhythm over long term .
Some of these drugs also have serious non cardiac side effects that limit its long term use in the management of atrial fibrillation .
Several new and investigational anti-arrhythmic agents are emerging but data supporting their effectiveness and safety are still limited .