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 .
Oral Propafenone To Convert Recent-Onset Atrial Fibrillation in Patients with and without Underlying Heart Disease
The optimal way to convert recent-onset atrial fibrillation to sinus rhythm is a subject of much debate . The effectiveness of intravenous propafenone  has been shown [ 1 - 3 ] , but the full antiarrhythmic effect of this regimen depends not only on the parent compound but on its 5-hydroxylated metabolite [ 4 , 5 ] . This dependence provides a strong rationale for the use of oral loading regimens [ 3 ] . Results of previous controlled studies have shown that oral loading of propafenone is highly effective in converting recent-onset atrial fibrillation to sinus rhythm [ 6 , 7 ] . Safety is a major concern with antiarrhythmic therapy . One of the primary proarrhythmic risks of propafenone and flecainide is the transformation of atrial fibrillation to flutter with 1:1 atrioventricular conduction and hemodynamic impairment [ 8 - 10 ] . We sought to determine whether the effectiveness and safety of propafenone differ in patients who have structural heart disease and patients who do not . Methods From June 1990 to June 1994 , consecutive patients with recent-onset atrial fibrillation ( 7 days ) who presented to one of three centers were considered for enrollment .  Onset of arrhythmia was documented by electrocardiography or by an abrupt onset of palpitations with subsequent evidence of atrial fibrillation on electrocardiography . Patients were excluded for any of the following reasons : age greater than 80 years , heart failure greater than NYHA ( New York Heart Association ) class II , mean ventricular rate during atrial fibrillation less than 70 beats/min , recent myocardial infa rct ion ( within < 6 months ) , unstable angina pectoris , previous or current electrocardiographic evidence ventricular preexcitation or complete bundle-branch block , previous electrocardiographic evidence of second- or third-degree atrioventricular block or bifascicular block , the sick sinus syndrome , hypokalemia ( potassium level < 3.5 mEq/L ) , renal or hepatic failure with severe hypoxia ( Pao 2 < 55 mm Hg ) , severe metabolic disturbances , or known thyroid dysfunction . Patients who were receiving long-term digoxin therapy or antiarrhythmic drugs or had received such treatments within 8 hours before study entry were also excluded . Patients who had atrial fibrillation that lasted 72 hours or longer were enrolled only if they were receiving long-term  warfarin therapy for anticoagulation . Patients provided informed consent . Eligible patients had a 24-hour Holter monitor applied ; after 1 to 2 hours of observation to assess the stability of atrial fibrillation , they were r and omly assigned by center in a single-blind manner to receive propafenone ( 300 mg in two tablets as a single oral dose ) or placebo . All patients received intravenous saline throughout the study period . The electrocardiogram was monitored by telemetry , blood pressure was measured every 2 hours , and 12-lead electrocardiography was done every hour for the first 4 hours and then every 2 hours for the next 4 hours . When patients converted to sinus rhythm , 12-lead electrocardiography was done immediately . Conversion was defined as a stable sinus rhythm that lasted for at least 1 hour . Eight hours after the study drug was administered , physicians could continue treatment with the study drug or switch to a different therapeutic option . Holter monitor tapes were analyzed by two blinded observers using computer scanning systems ( Marquette 8000 , Milwaukee , Wisconsin , and Del Mar Avionics , Irvine , California ) to determine the time of conversion to sinus rhythm and whether an abnormal rhythm was present . Within 24 hours after enrollment , echocardiography was done for each patient and left atrial diameter was measured in the left parasternal long-axis view . On the basis of clinical history and the results of physical examination , echocardiography , and chest radiography , patients were classified as having structural heart disease ( defined as the presence of cardiac abnormalities other than atrial fibrillation ) , hypertension without structural heart disease ( defined as previously recognized systemic hypertension according to the criteria of the World Health Organization ) , or neither . Continuous outcomes and baseline characteristics of the patients were compared by using the chi-square statistic and t-test as appropriate . The rates of conversion to sinus rhythm were assessed at 3 and 8 hours . Odds ratios and corresponding CIs were calculated according to the methods of Gardner and Altman [ 11 ] . We did logistic regression analysis to describe how the interaction of treatment with the presence or absence of heart disease and hypertension affected the probability of conversion to sinus rhythm . Analyses were done using SPS software , version 6.1.3 ( SPS , Inc. , Chicago , Illinois ) . Results Patients During the study period , 407 patients presented to the three centers and were screened for eligibility . Two hundred forty-three patients were eligible , and 240 gave consent . A total of 164 patients were excluded for one or more of the following reasons : age greater than 80 years ( n = 10 ) , heart failure greater than NYHA class II ( n = 33 ) , recent myocardial infa rct ion ( n = 20 ) , bundle-branch block ( n = 24 ) , the sick sinus syndrome ( n = 6 ) , severe hypoxia ( n = 13 ) , thyroid dysfunction ( n = 12 ) , and previous antiarrhythmic treatment ( n = 63 ) . Two hundred forty patients were r and omly assigned to receive propafenone ( n = 119 ) or placebo ( n = 121 ) . The two groups were similar with regard to age , sex , cause of atrial fibrillation , NYHA class , left atrial dimension ( measured by echocardiography ) , structural heart disease , and hypertension ( Table 1 ) . The duration of atrial fibrillation before r and omization ranged from 2.5 to 120 hours and did not differ significantly between the treatment groups . Table 1 . Patient Characteristics Conversion to Sinus Rhythm and Presence of Heart Disease The probability of conversion to sinus rhythm was greater after propafenone than after placebo at 3 and 8 hours ( P < 0.001 ) ( Figure 1 ) . Corresponding odds ratios were 3.8 ( 95 % CI , 2.1 to 6.8 ) at 3 hours and 5.4 ( CI , 3.0 to 9.4 ) at 8 hours . Figure 1 . Conversion to sinus rhythm within 8 hours in patients receiving propafenone or placebo . At 8 hours , the probability of conversion to sinus rhythm was significantly higher in the propafenone group than in the placebo group for patients who had heart disease ( odds ratio , 21.7 [ CI , 5.9 to 80.1 ] ; P < 0.001 ) , patients who had hypertension ( odds ratio , 6.4 [ CI , 2.3 to 17.6 ] ; P < 0.001 ) , and patients who did not have structural heart disease ( odds ratio , 2.8 [ CI , 1.2 to 6.7 ] ; P = 0.02 ) . Conversion rates at 8 hours for patients receiving propafenone were similar among the three heart disease subgroups , but conversion rates for patients receiving placebo differed significantly ( 56 % for patients without structural heart disease , 27 % for patients with hypertension , and 17 % patients with structural heart disease [ P = 0.009 by logistic regression model ] ) . At 3 hours , the probability of conversion to sinus rhythm was higher in the propafenone group than in the placebo group for patients who did not have heart disease ( 48 % for propafenone compared with 26 % for placebo ; odds ratio , 2.6 [ CI , 1.2 to 6.0 ] ; P = 0.02 ) , patients who had hypertension ( 41 % for propafenone compared with 16 % for placebo ; odds ratio , 3.5 [ CI , 1.2 to 10.5 ] ; P = 0.02 ) , and patients who had structural heart disease ( 47 % for propafenone compared with 7 % for placebo ; odds ratio , 12.3 [ CI , 2.5 to 60.5 ] ; P < 0.001 ) . By logistic regression analysis , no significant correlation between heart disease and treatment was seen at 3 hours ( P = 0.2 ) . Mean time SD for conversion to sinus rhythm within 8 hours was 181 118 minutes for propafenone and 181 112 minutes for placebo ( P > 0.2 ) . Adverse Effects Sustained atrial flutter or tachycardia ( lasting 1 min ) occurred in eight patients ( 7 % ) receiving propafenone and seven patients ( 6 % ) receiving placebo ( P > 0.2 ) , regardless of heart disease status . Among these patients , atrioventricular conduction was 2:1 in two patients receiving propafenone ( heart rate , 115 to 140 beats/min ) and three patients receiving placebo ( heart rate , 120 to 150 beats/min ) , 3:1 in six patients receiving propafenone ( heart rate , 60 to 95 beats/min ) and three patients receiving placebo ( heart rate , 60 to 100 beats/min ) , and 1:1 in one patient receiving placebo ( heart rate , 240 beats/min ) . This patient developed atrial flutter and collapsed . Pauses in ventricular rate lasting longer than 2 seconds were seen in one patient ( 1 % ) receiving propafenone and three patients ( 2 % ) receiving placebo ( P > 0.2 ) . Among patients receiving propafenone , nine ( 8 % ) had the following adverse effects : QRS complexes of the electrocardiogram greater than 120 ms ( n = 3 ) , hypotension ( n = 2 ) , slight hypotension and bradycardia at conversion ( n = 3 ) , and phases of junctional rhythm after conversion ( n = 1 ) . No ventricular proarrhythmic effects occurred . Discussion Oral loading of propafenone was effective for conversion to sinus rhythm in our study , as it has been in smaller studies [ 3 , 6 , 7 , 12 , 13 ] . The recent findings of Wijffels and colleagues [ 14 ] in a model of chronic atrial fibrillation in animals indicate that electrophysiologic remodeling occurs within a few hours of persistent atrial fibrillation and results primarily from changes in atrial refractoriness that enhance the persistence of atrial fibrillation . This observation provides a strong rationale for prompt conversion to sinus rhythm . Therefore , oral loading of propafenone ( which has an effectiveness similar to that of intravenous propafenone [ 3 ] ) offers many advantages over such regimens as oral quinidine and intravenous amiodarone , which require titration of dose or a longer period of time to achieve an effect [ 6 , 13 , 15 ] . In controlled trials , propafenone was shown to be more effective and to take effect more quickly than amiodarone [ 13 ] or digoxin plus quinidine [ 6 ] . Intravenous amiodarone  was no more effective than placebo
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 .