title: Candesartan in the prevention of relapsing atrial fibrillation. Optimal treatment strategy for patients with paroxysmal atrial fibrillation: J-RHYTHM Study. Comparative Evaluation of Effect of Valsartan/Amlodipine and Atenolol/Amlodipine Combinations on Atrial Fibrillation Recurrence in Hypertensive Patients With Type 2 Diabetes Mellitus Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. Effect of dronedarone on cardiovascular events in atrial fibrillation. Efficacy of Dofetilide in the Treatment of Atrial Fibrillation-Flutter in Patients With Reduced Left Ventricular Function: A Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) Substudy Increased mortality after dronedarone therapy for severe heart failure. Catheter ablation versus standard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation (CASTLE-AF) - study design. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. Incidence of Thromboembolic Events in Congestive Heart Failure Monitoring anticoagulation in atrial fibrillation Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. A randomised, controlled study of rate versus rhythm control in patients with chronic atrial fibrillation and heart failure: (CAFÉ-II Study) Comparison Of Digoxin Versus Low‐Dose Amiodarone For Ventricular Rate Control In Patients With Chronic Atrial Fibrillation Low- and medium-dose diltiazem in chronic atrial fibrillation: comparison with digoxin and correlation with drug plasma levels. Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy. Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study. Randomised trial of low-dose amiodarone in severe congestive heart failure Reliability of the PEDro scale for rating quality of randomized controlled trials. Rate control vs rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. The safety of amiodarone in patients with heart failure. Baseline quality of life as a predictor of mortality and hospitalization in 5,025 patients with congestive heart failure. SOLVD Investigations. Studies of Left Ventricular Dysfunction Investigators. Quality of life in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Morbidity and mortality among heart failure patients in Galicia, N.W. Spain: the GALICAP Study. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Valsartan for prevention of recurrent atrial fibrillation. Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial.
abstract: BACKGROUND Several studies have indicated that treatment with angiotensin converting enzyme ( ACE ) inhibitors and angiotensin II type 1 receptor blockers ( ARBs ) may reduce the incidence of atrial fibrillation ( AF ) in hypertensive patients and patients with left ventricular dysfunction . However , there is limited data on the effect of ACE-inhibitors and ARBs in patients undergoing electrical cardioversion for persistent AF . We hypothesized that treatment with the ARB c and esartan , without adjunct antiarrhythmic therapy , would reduce the recurrence rate of AF after successful cardioversion . METHODS In a double blind , placebo-controlled study , 171 patients with persistent AF were r and omized to receive c and esartan 8 mg once daily ( n=86 ) or placebo ( n=85 ) for 3 - 6 weeks before and c and esartan 16 mg once daily or placebo for 6 months after electrical cardioversion . Primary endpoint was recurrence of AF . RESULTS A total of 68 patients in the c and esartan group and 69 patients in the placebo group were successfully cardioverted . Forty-eight patients ( 71 % ) in the c and esartan group and 45 ( 65 % ) in the placebo group had a recurrence of AF during 6 months follow-up . Median time to recurrence was 8 and 9 days in the c and esartan and placebo groups , respectively . The differences between the groups were not statistically significant . CONCLUSION Treatment with the ARB c and esartan for 3 - 6 weeks before and 6 months after electrical cardioversion had no effect on the recurrence rate of AF Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation ( AF ) , the optimal treatment strategy for paroxysmal AF ( PAF ) remains unclear . Methods and Results A r and omized , multicenter comparison of rate control vs rhythm control in Japanese patients with PAF ( the Japanese Rhythm Management Trial for Atrial Fibrillation ( J-RHYTHM ) study ) was conducted . The primary endpoint was a composite of total mortality , symptomatic cerebral infa rct ion , systemic embolism , major bleeding , hospitalization for heart failure , or physical/psychological disability requiring alteration of treatment strategy . In the study , 823 patients with PAF were followed for a mean period of 578 days . The primary endpoint occurred in 64 patients ( 15.3 % ) assigned to rhythm control and in 89 patients ( 22.0 % ) to rate control ( P=0.0128 ) . No significant differences between the treatment strategies were observed in the incidences of death , stroke , bleeding and heart failure . Meanwhile , significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group , which was accompanied by improvement in AF-specific quality of life scores . Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control . However , mortality and cardiovascular morbidity were not affected by the treatment strategy ( umin-CTR No. C000000106 ) The aim of this study was to compare the effect of valsartan/amlodipine and atenolol/amlodipine combination in preventing the recurrence of atrial fibrillation ( AF ) in hypertensive diabetic patients with a history of recent paroxysmal atrial fibrillation . Two hundred ninty-six hypertensive patients with well-controlled type 2 diabetes in sinus rhythm but with at least 2 ECG-documented episodes of AF in the previous 6 months were r and omized to 160 mg of valsartan plus amlodipine ( titrated from 2.5 to 10 mg ) or to 100 mg of atenolol plus amlodipine ( 2.5 to 10 mg ) in addition to their previous antiarrhythmic treatment ( if any ) and were followed up for 1 year . Blood pressure ( BP ) and a 24-hour ECG were evaluated monthly . The patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible . SBP/DBP values were significantly reduced after 12 months with valsartan/amlodipine ( from 150.4/93.5 to 126.37/7.4 mm Hg , P < 0.001 ) and atenolol/amlodipine ( from 151.1/94.2 to 127.1/77.9 mm Hg , P < 0.001 ) , with no difference between the 2 regimens . At least 1 ECG-documented episode of AF was reported in 20.3 % of the patients treated with valsartan/amlodipine and in 34.1 % of those treated with atenolol/amlodipine , with a significant difference between treatments ( P < 0.01 ) . The positive effect of valsartan/amlodipine combination on AF recurrence was more evident in patients treated with amiodarone or propafenone than in patients treated with other antiarrhythmic drugs or without antiarrhythmic treatment . Despite similar BP reduction , valsartan/amlodipine combination was more effective in patients treated with amiodarone or propafenone than atenolol/amlodipine in preventing new episodes of AF in hypertensive diabetic patients BACKGROUND Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects .  Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects . METHODS In two identical multicenter , double-blind , r and omized trials , one conducted in Europe ( Clinical Trials.gov number , NCT00259428 [ Clinical Trials.gov ] ) and one conducted in the United States , Canada , Australia , South Africa , and Argentina ( termed the non-European trial , NCT00259376 [ Clinical Trials.gov ] ) , we evaluated the efficacy of dronedarone , with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo .  Rhythm was monitored transtelephonically on days 2 , 3 , and 5 ; at 3 , 5 , 7 , and 10 months ; during recurrence of arrhythmia ; and at nine scheduled visits during a 12-month period . The primary end point was the time to the first recurrence of atrial fibrillation or flutter . RESULTS In the European trial , the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group ( P=0.01 ) . The corresponding duration s in the non-European trial were 59 and 158 days ( P=0.002 ) . At the recurrence of arrhythmia in the European trial , the mean ( + /-SD ) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group ( P<0.001 ) ; the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute ( P<0.001 ) . Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group . CONCLUSIONS Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia BACKGROUND Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation . METHODS We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death . Patients were r and omly assigned to receive dronedarone , 400 mg twice a day , or placebo . The primary outcome was the first hospitalization due to cardiovascular events or death . Secondary outcomes were death from any cause , death from cardiovascular causes , and hospitalization due to cardiovascular events . RESULTS The mean follow-up period was 21+/-5 months , with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2 % ) receiving dronedarone and in 716 of the 2327 patients ( 30.8 % ) receiving placebo , mostly because of adverse events . The primary outcome occurred in 734 patients ( 31.9 % ) in the dronedarone group and in 917 patients ( 39.4 % ) in the placebo group , with a hazard ratio for dronedarone of 0.76 ( 95 % confidence interval [ CI ] , 0.69 to 0.84 ; P<0.001 ) . There were 116 deaths ( 5.0 % ) in the dronedarone group and 139 ( 6.0 % ) in the placebo group ( hazard ratio , 0.84 ; 95 % CI , 0.66 to 1.08 ; P=0.18 ) . There were 63 deaths from cardiovascular causes ( 2.7 % ) in the dronedarone group and 90 ( 3.9 % ) in the placebo group ( hazard ratio , 0.71 ; 95 % CI , 0.51 to 0.98 ; P=0.03 ) , largely due to a reduction in the rate of death from arrhythmia with dronedarone . The dronedarone group had higher rates of bradycardia , QT-interval prolongation , nausea , diarrhea , rash , and an increased serum creatinine level than the placebo group . Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups . CONCLUSIONS Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation . ( Clinical Trials.gov number , NCT00174785 . Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON  Dofetilide  ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P < 0.001 ) . Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P < 0.0001 ) . In addition , dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone , but it does not contain iodine and thus does not cause iodine-related adverse reactions . Therefore , it may be of value in the treatment of patients with heart failure . METHODS In a multicenter study with a double-blind design , we planned to r and omly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of  dronedarone twice a day or placebo . The primary end point was the composite of death from any cause or hospitalization for heart failure . RESULTS After inclusion of 627 patients ( 310 in the dronedarone group and 317 in the placebo group ) , the trial was prematurely terminated for safety reasons , at the recommendation of the data and safety monitoring board , in accordance with the board 's predefined rules for termination of the study . During a median follow-up of 2 months , 25 patients in the dronedarone group ( 8.1 % ) and 12 patients in the placebo group ( 3.8 % ) died ( hazard ratio in the dronedarone group , 2.13 ; 95 % confidence interval [ CI ] , 1.07 to 4.25 ; P=0.03 ) . The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group . The primary end point did not differ significantly between the two groups ; there were 53 events in the dronedarone group ( 17.1 % ) and 40 events in the placebo group ( 12.6 % ) ( hazard ratio , 1.38 ; 95 % CI , 0.92 to 2.09 ; P=0.12 ) . More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group . CONCLUSIONS In patients with severe heart failure and left ventricular systolic dysfunction , treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure . ( Clinical Trials.gov number , NCT00543699 . BACKGROUND Electrical isolation of the pulmonary veins by catheter ablation is an emerging treatment modality for the treatment of atrial fibrillation ( AF ) and is increasingly used in patients with heart failure . METHODS The catheter ablation versus st and ard conventional treatment in patients with left ventricular dysfunction and atrial fibrillation trial ( CASTLE-AF ) is a r and omized evaluation of ablative treatment of atrial fibrillation in patients with left ventricular dysfunction . The primary endpoint is the composite of all-cause mortality or worsening of heart failure requiring unplanned hospitalization using a time to first event analysis . Secondary endpoints are all-cause mortality , cardiovascular mortality , cerebrovascular accidents , worsening of heart failure requiring unplanned hospitalization , unplanned hospitalization due to cardiovascular reason , all-cause hospitalization , quality of life , number of therapies ( shock and antitachycardia pacing ) delivered by the implantable cardioverter-defibrillator ( ICD ) , time to first ICD therapy , number of device-detected ventricular tachycardia and ventricular fibrillation episodes , AF burden , AF free interval , left ventricular function , exercise tolerance , and percentage of right ventricular pacing . CASTLE-AF will r and omize 420 patients for a minimum of 3 years at 48 sites in the United States , Europe , Australia , and South America BACKGROUND Sudden death from cardiac causes remains a leading cause of death among patients with congestive heart failure ( CHF ) . Treatment with amiodarone or an implantable cardioverter-defibrillator ( ICD ) has been proposed to improve the prognosis in such patients . METHODS We r and omly assigned 2521 patients with New York Heart Association ( NYHA ) class II or III CHF and a left ventricular ejection fraction ( LVEF ) of 35 percent or less to conventional therapy for CHF plus placebo ( 847 patients ) , conventional therapy plus amiodarone ( 845 patients ) , or conventional therapy plus a conservatively programmed , shock-only , single-lead ICD ( 829 patients ) . Placebo and amiodarone were administered in a double-blind fashion . The primary end point was death from any cause . RESULTS The median LVEF in patients was 25 percent ; 70 percent were in NYHA class II , and 30 percent were in class III CHF . The cause of CHF was ischemic in 52 percent and nonischemic in 48 percent . The median follow-up was 45.5 months . There were 244 deaths ( 29 percent ) in the placebo group , 240 ( 28 percent ) in the amiodarone group , and 182 ( 22 percent ) in the ICD group . As compared with placebo , amiodarone was associated with a similar risk of death ( hazard ratio , 1.06 ; 97.5 percent confidence interval , 0.86 to 1.30 ; P=0.53 ) and ICD therapy was associated with a decreased risk of death of 23 percent ( 0.77 ; 97.5 percent confidence interval , 0.62 to 0.96 ; P=0.007 ) and an absolute decrease in mortality of 7.2 percentage points after five years in the overall population . Results did not vary according to either ischemic or nonischemic causes of CHF , but they did vary according to the NYHA class . CONCLUSIONS In patients with NYHA class II or III CHF and LVEF of 35 percent or less , amiodarone has no favorable effect on survival , whereas single-lead , shock-only ICD therapy reduces overall mortality by 23 percent Background The incidence of thromboembolism and the benefit of anticoagulation in congestive heart failure are controversial . Methods and Results The data base provided by the Veterans Affairs Vasodilator-Heart Failure Trials ( V-HeFT I and II ) was examined retrospectively to address these issues . In V-HeFT I , 642 men with heart failure were followed an average of 2.28 years , providing 1,464 patient-years of follow-up . In V-HeFT II , 804 men were followed an average of 2.56 years , with 2,061 patient-years of follow-up . Mean left ventricular ejection fraction was 30%o in V-HeFT I and 29 % in V-HeFT II . Functional capacity was at the interface of classes II and III with a peak exercise oxygen consumption of 14.7 mL. kg -1 . min-1 in V-HeFT I and 13.7 mL- kg-1 min-1 in V-HeFT II . Warfarin and antiplatelet agents were administered at the discretion of individual investigators . The incidence of all thromboembolic events during 1,068 patient-years without warfarin in V-HeFIT I was 2.7/100 patient-years and during 1,188 patient-years in V-HeFT II was 2.1/100 patient-years and was not reduced in patients treated with warfarin . Patients experiencing events had a lower peak exercise oxygen consumption ( P<0.03 in V-HeFT I and P<0.001 in V-HeFT II ) and a lower mean ejection fraction ( P=0.10 in V-HeFT I and P=0.07 in V-HeFT II ) . Atrial fibrillation was not associated with an increased risk of thromboembolic events . Conclusions The incidence of thromboembolism and stroke in class II or III congestive heart failure is not high and may not be significantly reduced with warfarin treatment . Routine use of anticoagulants in patients with heart failure may not be justified Abstract Background : R and omized control trials and observational studies show high- quality warfarin therapy leads to safe and effective stroke prophylaxis . In usual community practice , patient , physician and health care system factors are barriers to optimal anticoagulation . We examined the predictive relationship between inpatient and outpatient INR values in chronic non-valvular atrial fibrillation ( AF ) patients hospitalized for ischemic stroke ( S ) , bleed ( B ) and control events ( C ) in usual community practice . Methods : This nested case-control analysis identified AF patients hospitalized for S , B and C using medical and pharmacy cl aims spanning 4.5 years ( ‘ 98–‘03 ) and validating diagnosis with chart abstract ion . AF was defined as 2 medical cl aims for AF ≥ 42 days apart with a related prescription cl aim for warfarin . INRs from both outpatient and inpatient setting s were used to yield a continuous history of coagulation status . Time-in-therapeutic-range ( TTR ) was calculated by Rosendaal ’s linear interpolation method . Correlation of inpatient and prognostic utility of last outpatient INRs was tested with S or B hospitalizations using univariate and multivariate logistic regression . Results : Overall , 614 hospitalizations ( means : age 73.9 , CHADS2 = 3.24 ; 52 % male ) included S ( n = 98 ) , B ( n = 101 ) and C ( n = 415 ) events . Average TTR was 28.6 % ( 49.4 % at INR < 2.0 , 21.9 % at INR > 3.0 ) . First INR on admission ( INR < 2.0 or > 3.0 ) was associated with S and B hospitalizations ( OR-adjusted [ 95%CI ] , 1.68 [ 1.04–2.73 ] and 1.72 [ 1.02–2.90 ] ) , respectively . Last outpatient INR < 2.0 was not associated with S ( OR-adjusted [ 95%CI ] , 1.12 [ 0.77–1.81 ] ) , and INR > 3.0 was not associated with B ( OR-adjusted [ 95%CI ] , 1.25 [ 0.67–2.32 ] ) . Last outpatient INR measurement occurred at 28 , 22 and 24 days ( median ; S , B & C , respectively ) before hospitalization . Conclusion : Patients were observed within therapeutic range less than 30 % of their time on warfarin . While inpatient INRs were clearly associated with both ischemic stroke and bleed events , last outpatient INR before event was not predictive BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure . METHODS In this prospect i ve , multicenter clinical trial , we r and omly assigned patients with symptomatic , drug-resistant atrial fibrillation , an ejection fraction of 40 % or less , and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing .  All patients completed the Minnesota Living with Heart Failure question naire ( scores range from 0 to 105 , with a higher score indicating a worse quality of life ) and underwent echocardiography and a 6-minute walk test ( the composite primary end point ) . Over a 6-month period , patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation . RESULTS In all , 41 patients underwent pulmonary-vein isolation  , and 40 underwent atrioventricular-node ablation with biventricular pacing ; none were lost to follow-up at 6 months . The composite primary end point favored the group that underwent pulmonary-vein isolation , with an improved question naire score at 6 months ( 60 , vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing ; P<0.001 ) , a longer 6-minute-walk distance ( 340 m vs. 297 m , P<0.001 ) , and a higher ejection fraction ( 35 % vs. 28 % , P<0.001 ) . In the group that underwent pulmonary-vein isolation , 88 % of patients receiving antiarrhythmic drugs and 71 % of those not receiving such drugs were free of atrial fibrillation at 6 months . In the group that underwent pulmonary-vein isolation , pulmonary-vein stenosis developed in two patients , pericardial effusion in one , and pulmonary edema in another ; in the group that underwent atrioventricular-node ablation with biventricular pacing , lead dislodgment was found in one patient and pneumothorax in another . CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation . ( Clinical Trials.gov number , NCT00599976 . INTRODUCTION We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation ( AF ) . METHODS Five hundred and four amiodarone-naïve patients were r and omized to receive dronedarone 400 mg bid ( n = 249 ) or amiodarone 600 mg qd for 28 days then 200 mg qd ( n = 255 ) for at least 6 months . Primary composite endpoint was recurrence of AF ( including unsuccessful electrical cardioversion , no spontaneous conversion and no electrical cardioversion ) or premature study discontinuation . Main safety endpoint ( MSE ) was occurrence of thyroid- , hepatic- , pulmonary- , neurologic- , skin- , eye- , or gastrointestinal-specific events , or premature study drug discontinuation following an adverse event . RESULTS Median treatment duration was 7 months . The primary composite endpoint was 75.1 and 58.8 % with dronedarone and amiodarone , respectively , at 12 months ( hazard ratio [ HR ] 1.59 ; 95 % confidence interval [ CI ] 1.28 - 1.98 ; P < 0.0001 ) , mainly driven by AF recurrence with dronedarone compared with amiodarone ( 63.5 vs 42.0 % ) . AF recurrence after successful cardioversion was 36.5 and 24.3 % with dronedarone and amiodarone , respectively . Premature drug discontinuation tended to be less frequent with dronedarone ( 10.4 vs 13.3 % ) . MSE was 39.3 and 44.5 % with dronedarone and amiodarone , respectively , at 12 months ( HR = 0.80 ; 95 % CI 0.60 - 1.07 ; P = 0.129 ) , and mainly driven by fewer thyroid , neurologic , skin , and ocular events in the dronedarone group . CONCLUSION In this short-term study , dronedarone was less effective than amiodarone in decreasing AF recurrence , but had a better safety profile , specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants Background : Atrial fibrillation ( AF ) and heart failure ( HF ) often coexist . The aim was to investigate whether restoring sinus rhythm ( SR ) could improve cardiac function , symptoms , exercise capacity and quality of life ( QoL ) in patients with chronic heart failure . Methods : Patients with HF and persistent AF receiving guideline -recommended treatments , including anticoagulants , were eligible for the study . Patients were r and omised to either rhythm ( treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored ) or rate control . Anticoagulants were continued throughout the study regardless of rhythm , unless contraindications developed . Both groups were treated with beta blockers and /or digoxin to reduce the heart rate to < 80 bpm at rest and < 110 bpm after walking . Symptoms , walk distance ( 6-minute corridor walk test , 6MWT ) , QoL and cardiac function were assessed at baseline and 1 year . Results : 61 patients with HF and persistent AF ( median duration 14 months ( IQR 5 to 32 ) ) were r and omly assigned to a rate or rhythm control strategy . Of patients assigned to rhythm control ( n = 30 ) , 66 % were in SR at 1 year , and 90 % of those assigned to rate control ( n = 31 ) achieved the heart rate target . At 1 year , NYHA class ( p = 0.424 ) and 6MWT distance ( p = 0.342 ) were similar between groups but patients assigned to rhythm control had improved LV function ( p = 0.014 ) , NT-proBNP concentration ( p = 0.046 ) and QoL ( p = 0.019 ) compared with those assigned to rate control . Greatest improvement was seen in patients in whom SR was maintained . Conclusion : Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control 1 . Rapid ventricular rate ( VR ) and rhythm irregularity during atrial fibrillation ( AF ) impair cardiac performance . Although digoxin has been widely used in patients with AF , its efficacy for the control of VR and rhythm irregularity is unsatisfactory . Whether low‐dose amiodarone is more effective remains unclear The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation . The relationship between drug plasma levels and cardiovascular effects was also investigated . After 7 days of combined therapy with diltiazem ( 60 mg three times a day in 10 patients and four times a day in nine patients ) and digoxin ( 0.125 mg/day in two patients and 0.250 mg/day in 17 patients ) , the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3 % in comparison with digoxin therapy alone ; the serum digoxin level was not significantly changed ( 1.06 + /- 0.43 vs 1.05 + /- 0.61 ng/ml ) . After a st and ardized bicycle exercise test ( 50 watts for 3 minutes ) , maximal heart rate was reduced by 19.9 % , diastolic blood pressure was decreased by 8.9 % , and systolic pressure-rate product was decreased by 12.5 % . Diltiazem  plasma levels ( mean 120.9 + /- 63.3 ng/ml ) were linearly correlated with percentage variations in maximal heart rate , diastolic blood pressure , systolic blood pressure , and pressure-rate product during exercise . Eighteen patients in succession discontinued digoxin therapy ; after 14 days of diltiazem alone , the 24-hour mean heart rate returned to control values of digoxin therapy , whereas maximal heart rate and pressure-rate product during exercise were significantly reduced ( -17.2 % and -14.1 % , respectively ) , with no changes in blood pressure .  Diltiazem plasma levels ( 135.0 + /- 83.2 ng/ml ) showed a linear correlation with the percentage of reduction in maximal heart rate . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The purpose of this study was to determine quality of life ( QOL ) and exercise performance ( EP ) in patients with persistent atrial fibrillation ( AF ) converted to sinus rhythm ( SR ) compared with those remaining in or reverting to AF . BACKGROUND Restoration of SR in patients with AF improving QOL and EP remains controversial . METHODS Patients with persistent AF were r and omized double-blind to amiodarone , sotalol , or placebo . Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks ( n = 624 ) and 1 year ( n = 556 ) . The QOL ( SF-36 ) , symptom checklist ( SCL ) , specific activity scale ( SAS ) , AF severity scale ( AFSS ) , and EP were assessed . RESULTS Favorable changes were seen in SR patients at 8 weeks in physical functioning ( p < 0.001 ) , physical role limitations ( p = 0.03 ) , general health ( p = 0.002 ) , and vitality ( p < 0.001 ) , and at 1 year in general health ( p = 0.007 ) and social functioning ( p = 0.02 ) . Changes in the scores for SCL severity ( p = 0.01 ) , functional capacity ( p = 0.003 ) , and AFSS symptom burden ( p < 0.001 ) at 8 weeks and in SCL severity ( p < 0.01 ) and AF symptom burden ( p < 0.001 ) at 1 year showed significant improvements in SR versus AF . Symptomatic patients were more likely to have improvement . The EP in SR versus AF was greater from baseline to 8 weeks ( p = 0.01 ) and to 1 year ( p = 0.02 ) . The EP correlated with physical functioning and functional capacity except in the AF group at 1 year . CONCLUSIONS In patients with persistent AF , restoration and maintenance of SR was associated with improvements in QOL measures and EP . There was a strong correlation between QOL measures and EP BACKGROUND The present study aim ed to determine whether quality of life ( QOL ) in permanent atrial fibrillation ( AF ) patients would be improved by monotherapy with beta-blocker ( BB ) or calcium antagonist ( CAA ) as compared with digitalis . METHODS AND RESULTS Twenty-nine patients with permanent AF under digitalis were r and omized into BB ( bisoprolol , atenolol or metoprolol ) or CAA ( verapamil ) monotherapy treatment group . Twenty-five were men and the mean age was 67+/-8 years . After the assigned monotherapy , 12 patients received the other monotherapy in a cross-over fashion . Under each treatment , efficacy of rate control was determined by Holter electrocardiogram ( ECG ) , treadmill testing and QOL question naire ( Short Form-36 ( SF-36 ) and Quality of Life of Atrial Fibrillation ( AFQLQ ) ) , and compared with the baseline digitalis treatment . CAA significantly increased mean and minimum heart rate ( HR ) in Holter ECG as compared with digitalis , whereas BB increased only minimum HR . Exercise duration in treadmill testing was significantly prolonged by CAA treatment , although it only tended to be prolonged by BB treatment . CAA but not BB improved role function-physical score of SF-36 , and frequency and severity of symptoms of AFQLQ . CONCLUSION These results indicate that CAA is preferable to digitalis when monotherapy is selected for short-term improvement of QOL and exercise tolerance in patients with permanent AF In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias . The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure . Our prospect i ve multicentre trial included 516 patients on optimal st and ard treatment for heart failure . Patients were r and omised to 300 mg/day amiodarone ( 260 ) or to st and ard treatment ( 256 ) . Intention-to-treat analysis showed 87 deaths in the amiodarone group ( 33.5 % ) compared with 106 in the control group ( 41.4 % ) ( risk reduction 28 % ; 95 % CI 4%-45 % ; log rank test p = 0.024 ) . There were reductions in both sudden death ( risk reduction 27 % ; p = 0.16 ) and death due to progressive heart failure ( risk reduction 23 % ; p = 0.16 ) . Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure ( 119 versus 149 in the control group ; risk reduction 31 % ; 95 % CI 13 - 46 % ; p = 0.0024 ) . The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia . Side-effects were reported in 17 patients ( 6.1 % ) ; amiodarone was withdrawn in 12 . Low-dose amiodarone proved to be an effective and reliable treatment , reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . STUDY OBJECTIVES The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation ( AF ) remain to be fully explored . DESIGN The How to Treat Chronic Atrial Fibrillation ( HOT CAFE ) Polish trial was design ed to evaluate in a r and omized , multicenter , and prospect i ve manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF . PATIENTS Our study population comprised 205 patients ( 134 men and 71 women ; mean [ + /- SD ] age , 60.8 + /- 11.2 years ) with a mean AF duration of 273.7 + /- 112.4 days . The mean observation period was 1.7 + /- 0.4 years . One hundred one patients were r and omly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring . Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy . One hundred four patients were r and omized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen ( ie , disopyramide , propafenone , sotalol , and amiodarone ) . In both groups , thromboembolic prophylaxis followed current guidelines . MEASUREMENTS AND RESULTS At the end of follow-up , 63.5 % of patients in the rhythm control arm remained in sinus rhythm . No significant differences in the composite end point ( ie , all-cause mortality , number of thromboembolic events , or major bleeding ) were found between the rate control group and the rhythm control group ( odds ratio , 1.98 ; 95 % confidence interval , 0.28 to 22.3 ; p > 0.71 ) . The incidence of hospital admissions was much lower in the rate control arm ( 12 % vs 74 % , respectively ; p < 0.001 ) . New York Heart Association functional class improved in both study groups , while mean exercise tolerance , as measured by the maximal treadmill workload , improved only in the rhythm control group ( 5.2 + /- 5.1 vs 7.6 + /- 3.3 metabolic equivalents , respectively ; p < 0.001 ) . The rhythm control strategy led to an increased mean left ventricular fractional shortening ( 29 + /- 7 % vs 31 + /- 7 % , respectively ; p < 0.01 ) . One episode of pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy , while three patients in the rhythm control arm of the study experienced ischemic strokes ( not significant ) . CONCLUSIONS The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group 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 The impact of atrial fibrillation ( AF ) and its treatment on health-related quality of life ( QOL ) is not well understood . We assessed QOL in patients with symptomatic AF participating in the Canadian Trial of Atrial Fibrillation . METHODS Self-report QOL question naires including the Short-Form-36 ( SF-36 ) , symptom checklist ( SCL ) and AF Severity Scale ( AFSS ) were completed at baseline and 3 , and 12 months after r and omization . RESULTS The study group was aged 65 + /- 10 years and 59 % were male . By design , 50 % of patients were r and omized to amiodarone ( n = 132 ) , 25 % to sotalol ( n = 66 ) , and 25 % to propafenone ( n = 66 ) . Most patients had normal left ventricular function ( 89 % ) .  Physical ( 41.9 + /- 9.3 to 43.7 + /- 9.2 , P = .001 ) and mental health ( 47.5 + /- 10.5 to 49.0 + /- 9.8 , P = .023 ) summary measures from the SF-36 improved significantly from baseline to 3 months . Arrhythmia symptom frequency and severity ( SCL ) also improved markedly from baseline to 3 months ( symptom frequency 20.4 + /- 9.4 to 16.2 + /- 9.5 and symptom severity 16.7 + /- 8.2 to 12.9 + /- 7.4 , both P < .001 ) . QOL improvements were not significantly different among the groups r and omized to amiodarone , sotalol , or propafenone . However , patients with no symptomatic recurrences of AF had higher scores at 3 months on measures of global well-being than those with recurrences in the first 3 months ( 7.4 + /- 1.8 vs 6.9 + /- 1.8 , P < .05 ) . There were no significant QOL changes from the 3 to 12 month assessment . CONCLUSION In patients with symptomatic AF , QOL improves after treatment , independent of the specific drug used for treatment . This is especially true for patients in whom treatment prevents AF recurrence 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 Uncertainty persists about the safety and efficacy of amiodarone for the management of heart failure . METHODS AND RESULTS We r and omized 3029 patients with chronic heart failure to receive carvedilol or metoprolol  and followed patients for a median of 58 months . One hundred fifty-five of 1466 patients in New York Heart Association ( NYHA ) Class II and 209 of 1563 in Class III or IV received amiodarone at baseline . Persistence with amiodarone treatment was high and 66 % received amiodarone after 4 years . During follow-up , 38.7 % and 58.9 % of patients receiving amiodarone in NYHA Classes II and III + IV died versus 26.2 % and 43.3 % not receiving amiodarone ( P < .001 ) . This difference was maintained in multivariable analysis ( hazard ratio [ HR ] 1.5 , 95 % confidence interval [ CI ] 1.2 - 1.7 , P < .001 ) . The difference was explained by an increased risk of death due to circulatory failure ( HR 2.4 , CI 1.9 - 3.1 , P < .001 ) in patients receiving amiodarone .  Sudden death was not different ( HR 1.07 , CI 0.8 - 1.4 , P = .7 ) . The increased risk was similar across NYHA classes with HR of 1.60 ( CI 1.2 - 2.1 , P < .001 ) in NYHA Class II versus 1.58 ( CI 1.3 - 1.9 , P < .001 ) in Classes III + IV . CONCLUSIONS Treatment with amiodarone was associated with an increased risk of death from circulatory failure independent of functional class This study examined the independent relation of health-related quality of life ( HRQL ) to mortality and congestive heart failure (CHF)-related hospitalizations  in patients with an ejection fraction of < 0.35 followed for a mean of 36.5 months . A brief HRQL question naire was administered at baseline to patients r and omized to placebo or enalapril in the Studies of Left Ventricular Dysfunction ( SOLVD ) trial . Participants had an ejection fraction of < 0.35 and either symptomatic CHF ( treatment trial , n = 2,465 ) or asymptomatic CHF ( prevention trial , n = 2,560 ) . Baseline assessment of HRQL predicted mortality and CHF-related hospitalizations in symptomatic and asymptomatic patients r and omized to enalapril and placebo treatment . Domains that were the stronger univariate predictors of mortality and CHF-related hospitalizations were activities of daily living ( relative risk [ RR ] for mortality : 1.163 , p < 0.000 ; for hospitalization : 1.215 , p < 0.000 ) , general health ( RR for mortality : 1.205 , p < 0.000 ; for hospitalization : 1.188 , p < 0.000 ) , and social functioning ( RR for mortality 1.098 , p < 0.000 ; for hospitalization : RR 1.156 , p < 0.000 ) . In the multivariate model , activities of daily living ( RR for mortality 1.41 , p < 0.000 ; for hospitalization : RR 1.43 , p < 0.002 ) , general health ( RR for mortality 1.21 , p < 0.000 ; for hospitalization RR 1.16 , p < 0.013 ) and heart failure symptoms ( RR for mortality 1.02 , p < 0.025 ; for hospitalization RR 1.03 , p < 0.004 ) were found to be independent risk factors . HRQL independently predicted mortality and CHF-related hospitalizations after adjustment for ejection fraction , age , treatment , and New York Heart Association classification in patients with an ejection fraction of < 0.35 , r and omized to enalapril and placebo treatment . HRQL provides additional clinical information regarding disease course and outcome that is not captured by traditional indexes of clinical status OBJECTIVE The objective of this prespecified sub study of the AFFIRM study , in which no differences in survival or event rates were found in patients with atrial fibrillation ( AF ) r and omized to either rate control or rhythm control , was to test the null hypothesis that quality of life ( QoL ) is equal with rate- versus rhythm-control treatment strategies in AF . METHODS Fifty-six ( 25 % ) of AFFIRM sites were r and omly selected to recruit AFFIRM patients for the QoL sub study . Instruments used in the QoL assessment were ( 1 ) Perceived Health ;  ( 2 ) the  Cantril Ladder of Life ;  ( 3 ) the  Short Form 36 survey ;  ( 4 ) the  QoL Index ;  and ( 5 ) the  Symptom Checklist : Frequency and Severity .  Data were collected at baseline , 2 months , 12 months , and annually ; data are reported through 4 years of follow-up . RESULTS Baseline characteristics of the AFFIRM QoL patients ( n = 716 ) were generally similar to those of the rest of AFFIRM patients .  Quality -of-life scores were similar in rate- and rhythm-control assignment groups at all time points . Quality -of-life scores were similar whether the actual rhythm was sinus or AF . Scores increased from baseline to subsequent time points similarly for both groups ; these improvements were not additive over time . CONCLUSIONS Quality of life was comparable between rate- and rhythm-control treatment strategies . In addition , QoL was similar with sinus rhythm versus AF . Attempts to improve QoL by restoring sinus rhythm will usually be unsuccessful OBJECTIVE Characterization of current morbidity and mortality among heart failure ( HF ) out patients in Galicia ( N.W. Spain ) , together with their main determinants . DESIGN Prospect i ve multicentre study involving 149 primary care physicians . SETTING Primary care physicians selected r and omly from among all ( 1959 ) primary care physicians in Galicia . PATIENTS Clinical and epidemiological information for 1195 out patients with HF were collected in 2006 , with a mean follow-up of 6.5+/-1.5 months . MAIN OUTCOME MEASURES Survival rates were calculated by Cox 's proportional hazard model . RESULTS Mean patient age was 76 years , 48 % were male , 82 % had a history of arterial hypertension , and 32 % ischaemic cardiopathy . Echocardiography had been performed in 67 % , showing preserved systolic function in 61 % . Ninety-two ( 8 % ) died during follow-up [ 74 ( 80 % ) of them from cardiac causes ] , and 313 ( 29 % ) were re-admitted to hospital [ 230 ( 73 % ) of them for cardiac reasons ] . Multivariate analysis identified the following independent predictors of cardiovascular death and /or readmission : ischaemic cardiopathy [ hazard ratio ( HR ) 1.76 , 95 % confidence interval ( CI ) 1.29 - 4.40 ] , stroke ( HR 1.79 , CI 1.18 - 2.73 ) , oedema ( HR 1.49 , CI 1.10 - 2.03 ) , anaemia ( HR 1.66 , CI 1.21 - 2.27 ) , deteriorated systolic function ( HR 1.62 , CI 1.19 - 2.20 ) , and previous cardiovascular admissions ( HR 2.33 , CI 1.67 - 3.24 ) . Residence in the Barbanza district was identified as an independent predictor of survival free from cardiovascular admission ( HR 0.56 , CI 0.37 - 0.86 ) . CONCLUSION Morbidity and mortality are currently high among Galician HF patients , and their best single predictor is previous hospitalization for cardiovascular reasons 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 Atrial fibrillation is the most common cardiac arrhythmia , and no current therapy is ideal for control of this condition . Experimental studies suggest that angiotensin II-receptor blockers ( ARBs ) can influence atrial remodeling , and some clinical studies suggest that they may prevent atrial fibrillation . METHODS We conducted a large , r and omized , prospect i ve , placebo-controlled , multicenter trial to test whether the ARB valsartan could reduce the recurrence of atrial fibrillation . We enrolled patients who were in sinus rhythm but had had either two or more documented episodes of atrial fibrillation in the previous 6 months or successful cardioversion for atrial fibrillation in the previous 2 weeks . To be eligible , patients also had to have underlying cardiovascular disease , diabetes , or left atrial enlargement . Patients were r and omly assigned to receive valsartan or placebo . The two primary end points were the time to a first recurrence of atrial fibrillation and the proportion of patients who had more than one recurrence of atrial fibrillation over the course of 1 year . RESULTS A total of 1442 patients were enrolled in the study .  Atrial fibrillation recurred in 371 of the 722 patients ( 51.4 % ) in the valsartan group , as compared with 375 of 720 ( 52.1 % ) in the placebo group ( adjusted hazard ratio , 0.97 ; 96 % confidence interval [ CI ] , 0.83 to 1.14 ; P=0.73 ) . More than one episode of atrial fibrillation occurred in 194 of 722 patients ( 26.9 % ) in the valsartan group and in 201 of 720 ( 27.9 % ) in the placebo group ( adjusted odds ratio , 0.89 ; 99 % CI , 0.64 to 1.23 ; P=0.34 ) . The results were similar in all predefined subgroups of patients , including those who were not receiving angiotensin-converting-enzyme inhibitors . CONCLUSIONS Treatment with valsartan was not associated with a reduction in the incidence of recurrent atrial fibrillation . ( Clinical Trials.gov number , NCT00376272 . Post hoc analyses of the Digitalis Investigation Group ( DIG ) trial indicate that digoxin at low ( 0.5 to 0.9 ng/ml ) serum digoxin concentration ( SDC ) reduces mortality , which is eliminated at higher ( > or=1 ng/ml ) SDC , and that low-dose digoxin ( < or=0.125 mg/day ) predicts low SDC . In the DIG trial , patients with ambulatory chronic systolic and diastolic heart failure ( HF ) ( n = 7,788 ) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were r and omized to receive placebo ( n = 3,899 ) or digoxin ( n = 3,889 ) . The median dose of digoxin ( 0.25 mg/day ) and the target SDC ( 0.8 to 2.5 ng/ml ) were higher than what are currently recommended , which in part may explain the lack of long-term mortality benefit of digoxin in the DIG trial . To test this hypothesis , we examined the effect of digoxin on short-term outcomes ; 1-year all-cause mortality occurred in 392 and 448 patients respectively in the digoxin and placebo groups ( hazard ratio for digoxin 0.87 , 95 % confidence interval [ CI ] 0.76 to 0.995 , p = 0.043 ) . Respective hazard ratios for cardiovascular and HF deaths were 0.87 ( 95 % CI 0.76 to 1.01 , p = 0.072 ) and 0.66 ( 95 % CI 0.52 to 0.85 , p = 0.001 ) . All-cause hospitalization occurred in 1,411 and 1,529 patients receiving digoxin and placebo respectively ( hazard ratio 0.89 , 95 % CI 0.83 to 0.96 , p = 0.002 ) . Respective hazard ratios for cardiovascular and HF hospitalizations were 0.82 ( 95 % CI 0.75 to 0.89 , p < 0.0001 ) and 0.59 ( 95 % CI 0.52 to 0.66 , p < 0.0001 ) . In conclusion , digoxin reduced 1-year mortality and hospitalization in patients with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics . R and omized clinical trials are needed to determine the effect of low-dose digoxin in contemporary patients with chronic HF
target: In patients with AF and HF , rate control compared with rhythm control showed inferior risk of hospitalisation
background: BACKGROUND Atrial fibrillation ( AF ) is a common arrhythmia that can promote or worsen heart failure ( HF ) .
  Our purpose was to compare the effects of rate and rhythm control in patients with atrial fibrillation and heart failure .