human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Atrial fibrillation ( AF ) shortens the atrial effective refractory period ( ERP ) and predisposes to further episodes of AF . The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload . The purpose of this study was to determine whether digoxin , which increases intracellular calcium , potentiates the acute effects of AF on atrial refractoriness in humans . Methods and Results In 38 healthy adults , atrial ERP was measured at basic drive cycle lengths ( BDCLs ) of 350 and 500 ms after autonomic blockade . Nineteen patients had been treated with digoxin for 2 weeks . After a several-minute episode of AF , atrial ERP was measured serially at alternating BDCLs . Compared with pre-AF ERPs , the first post-AF ERPs were significantly shorter in both the digoxin and the control groups ( P < 0.001 ) . The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group ( 37±16 ms ) than in the control group ( 20±13 ms , P < 0.001 ) ; similar changes occurred at a BDCL of 500 ms . During post-AF determinations of the atrial ERP , secondary AF episodes occurred significantly more often in the digoxin group ( 32 % versus 16%;P < 0.04 ) . Conclusions After a brief episode of AF , digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF . These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects Background —Postoperative atrial arrhythmias are common and are associated with considerable morbidity . This study was design ed to evaluate the efficacy and safety of vernakalant for the conversion of  atrial fibrillation ( AF ) or  atrial flutter ( AFL ) after cardiac surgery . Methods and Results —This was a prospect i ve , r and omized , double-blind , placebo-controlled trial of vernakalant for the conversion of AF or AFL  after coronary artery bypass graft , valvular surgery , or both . Patients were r and omly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo . If AF or AFL was present after a 15-minute observation period , then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given . The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing . In patients with AF , 47 of 100 ( 47 % ) who received vernakalant converted to SR compared with 7 of 50 ( 14 % ) patients who received placebo ( P<0.001 ) . The median time to conversion was 12 minutes . Vernakalant was not effective in converting postoperative AFL to sinus rhythm . Two serious adverse events occurred within 24 hours of vernakalant administration ( hypotension and complete atrioventricular block ) . There were no cases of torsades de pointes , sustained ventricular tachycardia , or ventricular fibrillation . There were no deaths . Conclusions —Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery . Clinical Trial Registration — clinical trials.gov . Identifier : NCT00125320 BACKGROUND Patients with rheumatic heart disease and atrial fibrillation incur significant morbidity and mortality . It is not known which approach , rate control or maintenance of sinus rhythm might be most appropriate . The present study was undertaken to compare the strategy of ventricular rate control versus maintenance of sinus rhythm in rheumatic atrial fibrillation , and to evaluate the role of amiodarone in this patient population . METHODS AND RESULTS We prospect ively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol -rhythm control ( group I : 48 patients each with amiodarone -group Ia ; and  placebo -group  Ib ) and compared the effects with the ventricular rate control ( group II ) by diltiazem ( n=48 , open-label ) . Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6+/-10.3 years , left atrial size was 4.7+/-0.6 cm , atrial fibrillation duration was 6.1+/-5.4 years , and 72.9 % patients had undergone valvular interventions . At 1 year , 45 patients with sinus rhythm in group I compared to 48 patients in group II demonstrated significant increase in exercise to sinus rhythm time , had improvement in functional class and quality of life score . There was no difference in hospitalization rates , systemic bleeds or incidence of thromboembolism . Five patients died in group II but none in group I ( p=0.02 ) . In group I , 73/87 ( 83.9 % ) patients converted , and 45/86 ( 52.3 % ) patients maintained sinus rhythm at 1 year . Conversion rates were 38/43 ( 88.4 % ) with amiodarone versus 34/44 ( 77.3 % ) with placebo ( p=0.49 ) : corresponding rate for maintaining sinus rhythm was 29/42 ( 69.1 % ) versus 16/44 ( 36.4 % ) , p=0.008 respectively . CONCLUSIONS Maintenance of sinus rhythm appeared to be superior to ventricular rate control in patients with rheumatic atrial fibrillation in terms of an effect on mortality and morbidity . Sinus rhythm could be restored in the majority and amiodarone was superior to placebo in this regard Dofetilide may be advantageous in terminating  atrial fibrillation/atrial flutter ( AFl )  when there are contraindications for class I drugs ( left ventricular dysfunction and /or manifest myocardial ischemia ) and beta blockers . In particular , its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl Background —Atrial fibrillation ( AF ) has a deleterious impact on health-related quality -of-life ( HRQoL ) , but measuring this outcome is difficult . A comprehensive , vali date d , disease-specific question naire to measure the spectrum of QoL domains affected by AF and its treatment is not available . We developed and vali date d a 20-item question naire , Atrial Fibrillation Effect on QualiTy -of-life ( AFEQT ) , in a 6-center , prospect i ve , observational study . Methods and Results —Factor analyses established 4 conceptual domains ( Symptoms , Daily Activities , Treatment Concern , and Treatment Satisfaction ) from which individual domain and global scores were calculated . Participants from 6 centers completed the AFEQT at baseline , at month 1 , and at month 3 . Psychometric analyses included internal consistency and known-group validity . Test-retest reliability was assessed by comparing 1-month changes in scores among those with no change in therapy . Effect size was used to assess responsiveness after intervention . Among 219 patients age 62±11.9 years , 94 % completed the AFEQT at baseline and 3 months ; 66 % had paroxysmal , 24 % persistent , 5 % longst and ing persistent , and 5 % permanent AF .  Internal consistency was > 0.88 for all scales . Lower AFEQT scores were observed with increased AF severity , categorized as asymptomatic , mild , moderate and severe , respectively : 71.2±20.6 , 71.3±19.2 , 57.9±19.0 , and 42.0±21.2 . Intraclass correlations for Overall , Symptoms , Daily Activities , Treatment Concern , and Satisfaction scores were 0.8 , 0.5 , 0.8 , 0.7 , and 0.7 , respectively . Changes in 3-month scores were larger after ablation than with pharmacological adjustments , and both were greater than those observed in stable patients . Conclusions —This initial validation of AFEQT supports its use as an outcome in studies and a means to clinical ly follow patients with 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 ) Background Rapid conversion of  atrial fibrillation ( AF ) to sinus rhythm may be achieved by the administration of class IA , IC and III antiarrhythmic drugs or vernakalant hydrochloride . However , that treatment may be related to potential pro-arrhythmia , lack of efficacy or the exceptionally high cost of a compound used . Antazoline is a first generation antihistaminic agent with chinidin-like properties . When administered intravenously , antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia , especially on AF , facilitating rapid conversion to sinus rhythm . Despite a relative lack of published data antazoline has been marketed in Pol and and widely used in cardiology wards and emergency rooms for many years due to its efficacy , safety and rapid onset of action within minutes of administration . Methods / design A r and omized , double blind , placebo-controlled , superiority clinical trial was design ed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm .  Eligible patients will present AF lasting less than 43 hours , will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease . Long-term antiarrhythmic therapy is not considered an exclusion criterion . Subjects who fulfill selection criteria will be r and omly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v . bolus . Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram ( ECG ) during the observation period . Secondary end points will be comprised of time to conversion and return of AF during the observation period . Special consideration will be given to the observation of any adverse events . A sample size of 80 patients was calculated based on the following assumptions : two-tailed test , a type I error of 0.01 , a power of 90 % , efficacy of placebo 5 % , efficacy of antazoline 50 % and 20 % drop-out rate to fulfill the criteria of intention-to-treat analysis . Due to the presumed lack of statistical power , the secondary end points and safety endpoints will be considered exploratory . Clinical trials registry Clinical Trials.gov , Objective Ibutilide , a class III antiarrhythmic drug , has been shown to convert atrial fibrillation to sinus rhythm more rapidly than procainamide or sotalol . Our objective was to compare the efficacy and safety of ibutilide and amiodarone in patients after cardiac surgery . Design Prospect i ve , r and omized , double-blinded study . Setting Intensive care unit of a university hospital . Patients Forty adults with an onset of atrial fibrillation within 3 hrs after admission . Interventions Before the administration of antiarrhythmic drugs , a 24-hr Holter electrocardiograph was attached . Patients in the ibutilide group received ibutilide 0.008 mg/kg body weight over 10 mins ; treatment was repeated if atrial fibrillation or flutter persisted . If sinus rhythm was not achieved within 4 hrs , amiodarone 5 mg/kg was administered over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs . Patients in the amiodarone group received amiodarone 5 mg/kg over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs if atrial fibrillation or flutter continued . Measurements and Main Results Within the first 4 hrs , atrial fibrillation was converted in nine of 20 patients ( 45 % ) in group ibutilide and in ten of 20 patients ( 50 % ) in group amiodarone ( not significant ) . Mean time for conversion overall was 385 mins in group ibutilide and 495 mins in group amiodarone ( not significant ) . In group am 
    Output:
    
agent
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 .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Atrial fibrillation ( AF ) shortens the atrial effective refractory period ( ERP ) and predisposes to further episodes of AF . The acute changes in atrial refractoriness may be related to tachycardia-induced intracellular calcium overload . The purpose of this study was to determine whether digoxin , which increases intracellular calcium , potentiates the acute effects of AF on atrial refractoriness in humans . Methods and Results In 38 healthy adults , atrial ERP was measured at basic drive cycle lengths ( BDCLs ) of 350 and 500 ms after autonomic blockade . Nineteen patients had been treated with digoxin for 2 weeks . After a several-minute episode of AF , atrial ERP was measured serially at alternating BDCLs . Compared with pre-AF ERPs , the first post-AF ERPs were significantly shorter in both the digoxin and the control groups ( P < 0.001 ) . The post-AF ERP at a BDCL of 350 ms shortened to a greater degree in the digoxin group ( 37±16 ms ) than in the control group ( 20±13 ms , P < 0.001 ) ; similar changes occurred at a BDCL of 500 ms . During post-AF determinations of the atrial ERP , secondary AF episodes occurred significantly more often in the digoxin group ( 32 % versus 16%;P < 0.04 ) . Conclusions After a brief episode of AF , digoxin augments the shortening that occurs in atrial refractoriness and predisposes to the reinduction of AF . These effects occur in the setting of autonomic blockade and therefore are more likely to be due to the effects of digoxin on intracellular calcium than to its vagotonic effects Background —Postoperative atrial arrhythmias are common and are associated with considerable morbidity . This study was design ed to evaluate the efficacy and safety of vernakalant for the conversion of  atrial fibrillation ( AF ) or  atrial flutter ( AFL ) after cardiac surgery . Methods and Results —This was a prospect i ve , r and omized , double-blind , placebo-controlled trial of vernakalant for the conversion of AF or AFL  after coronary artery bypass graft , valvular surgery , or both . Patients were r and omly assigned 2:1 to receive a 10-minute infusion of 3 mg/kg vernakalant or placebo . If AF or AFL was present after a 15-minute observation period , then a second 10-minute infusion of 2 mg/kg vernakalant or placebo was given . The primary end point was the conversion of postcardiac surgery AF or AFL to sinus rhythm within 90 minutes of dosing . In patients with AF , 47 of 100 ( 47 % ) who received vernakalant converted to SR compared with 7 of 50 ( 14 % ) patients who received placebo ( P<0.001 ) . The median time to conversion was 12 minutes . Vernakalant was not effective in converting postoperative AFL to sinus rhythm . Two serious adverse events occurred within 24 hours of vernakalant administration ( hypotension and complete atrioventricular block ) . There were no cases of torsades de pointes , sustained ventricular tachycardia , or ventricular fibrillation . There were no deaths . Conclusions —Vernakalant was safe and effective in the rapid conversion of AF to sinus rhythm in patients who had AF after cardiac surgery . Clinical Trial Registration — clinical trials.gov . Identifier : NCT00125320 BACKGROUND Patients with rheumatic heart disease and atrial fibrillation incur significant morbidity and mortality . It is not known which approach , rate control or maintenance of sinus rhythm might be most appropriate . The present study was undertaken to compare the strategy of ventricular rate control versus maintenance of sinus rhythm in rheumatic atrial fibrillation , and to evaluate the role of amiodarone in this patient population . METHODS AND RESULTS We prospect ively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol -rhythm control ( group I : 48 patients each with amiodarone -group Ia ; and  placebo -group  Ib ) and compared the effects with the ventricular rate control ( group II ) by diltiazem ( n=48 , open-label ) . Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6+/-10.3 years , left atrial size was 4.7+/-0.6 cm , atrial fibrillation duration was 6.1+/-5.4 years , and 72.9 % patients had undergone valvular interventions . At 1 year , 45 patients with sinus rhythm in group I compared to 48 patients in group II demonstrated significant increase in exercise to sinus rhythm time , had improvement in functional class and quality of life score . There was no difference in hospitalization rates , systemic bleeds or incidence of thromboembolism . Five patients died in group II but none in group I ( p=0.02 ) . In group I , 73/87 ( 83.9 % ) patients converted , and 45/86 ( 52.3 % ) patients maintained sinus rhythm at 1 year . Conversion rates were 38/43 ( 88.4 % ) with amiodarone versus 34/44 ( 77.3 % ) with placebo ( p=0.49 ) : corresponding rate for maintaining sinus rhythm was 29/42 ( 69.1 % ) versus 16/44 ( 36.4 % ) , p=0.008 respectively . CONCLUSIONS Maintenance of sinus rhythm appeared to be superior to ventricular rate control in patients with rheumatic atrial fibrillation in terms of an effect on mortality and morbidity . Sinus rhythm could be restored in the majority and amiodarone was superior to placebo in this regard Dofetilide may be advantageous in terminating  atrial fibrillation/atrial flutter ( AFl )  when there are contraindications for class I drugs ( left ventricular dysfunction and /or manifest myocardial ischemia ) and beta blockers . In particular , its successful outcome in usually drug-resistant AFl is promising and underscores the importance of selective class III action for terminating AFl Background —Atrial fibrillation ( AF ) has a deleterious impact on health-related quality -of-life ( HRQoL ) , but measuring this outcome is difficult . A comprehensive , vali date d , disease-specific question naire to measure the spectrum of QoL domains affected by AF and its treatment is not available . We developed and vali date d a 20-item question naire , Atrial Fibrillation Effect on QualiTy -of-life ( AFEQT ) , in a 6-center , prospect i ve , observational study . Methods and Results —Factor analyses established 4 conceptual domains ( Symptoms , Daily Activities , Treatment Concern , and Treatment Satisfaction ) from which individual domain and global scores were calculated . Participants from 6 centers completed the AFEQT at baseline , at month 1 , and at month 3 . Psychometric analyses included internal consistency and known-group validity . Test-retest reliability was assessed by comparing 1-month changes in scores among those with no change in therapy . Effect size was used to assess responsiveness after intervention . Among 219 patients age 62±11.9 years , 94 % completed the AFEQT at baseline and 3 months ; 66 % had paroxysmal , 24 % persistent , 5 % longst and ing persistent , and 5 % permanent AF .  Internal consistency was > 0.88 for all scales . Lower AFEQT scores were observed with increased AF severity , categorized as asymptomatic , mild , moderate and severe , respectively : 71.2±20.6 , 71.3±19.2 , 57.9±19.0 , and 42.0±21.2 . Intraclass correlations for Overall , Symptoms , Daily Activities , Treatment Concern , and Satisfaction scores were 0.8 , 0.5 , 0.8 , 0.7 , and 0.7 , respectively . Changes in 3-month scores were larger after ablation than with pharmacological adjustments , and both were greater than those observed in stable patients . Conclusions —This initial validation of AFEQT supports its use as an outcome in studies and a means to clinical ly follow patients with 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 ) Background Rapid conversion of  atrial fibrillation ( AF ) to sinus rhythm may be achieved by the administration of class IA , IC and III antiarrhythmic drugs or vernakalant hydrochloride . However , that treatment may be related to potential pro-arrhythmia , lack of efficacy or the exceptionally high cost of a compound used . Antazoline is a first generation antihistaminic agent with chinidin-like properties . When administered intravenously , antazoline exerts a strong antiarrhythmic effect on supraventricular arrhythmia , especially on AF , facilitating rapid conversion to sinus rhythm . Despite a relative lack of published data antazoline has been marketed in Pol and and widely used in cardiology wards and emergency rooms for many years due to its efficacy , safety and rapid onset of action within minutes of administration . Methods / design A r and omized , double blind , placebo-controlled , superiority clinical trial was design ed to assess clinical efficacy of antazoline in rapid conversion of AF to sinus rhythm .  Eligible patients will present AF lasting less than 43 hours , will be in stable cardio-pulmonary condition and will have no prior history of advanced heart failure or significant valvular disease . Long-term antiarrhythmic therapy is not considered an exclusion criterion . Subjects who fulfill selection criteria will be r and omly assigned to receive intravenously either antazoline or placebo in divided doses and observed for 1.5 hours after conversion to sinus rhythm or after the last i.v . bolus . Primary end point will be the conversion of AF to sinus rhythm confirmed in an electrocardiogram ( ECG ) during the observation period . Secondary end points will be comprised of time to conversion and return of AF during the observation period . Special consideration will be given to the observation of any adverse events . A sample size of 80 patients was calculated based on the following assumptions : two-tailed test , a type I error of 0.01 , a power of 90 % , efficacy of placebo 5 % , efficacy of antazoline 50 % and 20 % drop-out rate to fulfill the criteria of intention-to-treat analysis . Due to the presumed lack of statistical power , the secondary end points and safety endpoints will be considered exploratory . Clinical trials registry Clinical Trials.gov , Objective Ibutilide , a class III antiarrhythmic drug , has been shown to convert atrial fibrillation to sinus rhythm more rapidly than procainamide or sotalol . Our objective was to compare the efficacy and safety of ibutilide and amiodarone in patients after cardiac surgery . Design Prospect i ve , r and omized , double-blinded study . Setting Intensive care unit of a university hospital . Patients Forty adults with an onset of atrial fibrillation within 3 hrs after admission . Interventions Before the administration of antiarrhythmic drugs , a 24-hr Holter electrocardiograph was attached . Patients in the ibutilide group received ibutilide 0.008 mg/kg body weight over 10 mins ; treatment was repeated if atrial fibrillation or flutter persisted . If sinus rhythm was not achieved within 4 hrs , amiodarone 5 mg/kg was administered over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs . Patients in the amiodarone group received amiodarone 5 mg/kg over 30 mins , followed by amiodarone 15 mg/kg over 24 hrs if atrial fibrillation or flutter continued . Measurements and Main Results Within the first 4 hrs , atrial fibrillation was converted in nine of 20 patients ( 45 % ) in group ibutilide and in ten of 20 patients ( 50 % ) in group amiodarone ( not significant ) . Mean time for conversion overall was 385 mins in group ibutilide and 495 mins in group amiodarone ( not significant ) . In group am 
    Output:
    