Conversion and maintenance of sinus rhythm by bepridil in patients with persistent atrial fibrillation.

BACKGROUND: Bepridil has multiple ion-channel blocking effects similar to amiodarone and is expected to have anti-arrhythmic effects that are useful for the management of atrial fibrillation (AF). The aim of this study was to clarify the conversion of persistent AF and maintenance of sinus rhythm (SR) by oral bepridil. METHODS AND RESULTS: Oral bepridil was administered to 112 patients (83 males, 29 females; age: 59.0+/-10.8 years) with persistent AF lasting an average of 5 months. The conversion effects and maintenance of SR after pharmacological or direct current (DC) cardioversion, as well as the incidence of adverse complications, were evaluated. In 65 of 112 (58%) patients, SR was restored within 6 months (average: 2.1 months) following bepridil administration. DC cardioversion was carried out for 21 of the remaining 47 patients with unsuccessful pharmacological conversion, and all had restoration of SR. Eventually, of the 86 patients in total who were restored to SR by either bepridil or DC cardioversion, 70 (81%) patients maintained SR after a mean follow-up of 18 months. No serious adverse complications were observed, except for marked QT prolongation in 2 cases. CONCLUSION: Bepridil showed favorable conversion effects in patients with persistent AF and was highly effective for maintaining SR after pharmacological or electrical cardioversion. However, careful follow-up is necessary for the prevention of torsade de pointes caused by QT prolongation.     

Atrial fibrillatory rate and sinus rhythm maintenance in patients undergoing cardioversion of persistent atrial fibrillation.

AIMS: The study set out to explore whether an index of atrial electrical electrophysiology can be used to predict atrial fibrillation (AF) relapse, and if the predictive properties differ as a result of arrhythmia duration. METHODS AND RESULTS: The study comprised 175 consecutive patients with persistent AF (median duration 94 days, range 2 to 1044) referred for cardioversion. Twenty-nine patients had arrhythmia duration under 30 days (median 5 days, range 2-26). Atrial fibrillatory rate (AFR) was estimated using a frequency power spectrum analysis of QRST-cancelled ECG. At 1-month follow-up, 56% of the patients had relapsed to AF. The pre-cardioversion mean AFR of those patients was 399+/-52 fibrillations per minute (fpm) compared with 363+/-63 fpm among patients maintaining SR (P<0.0001). In patients with short AF duration, the difference was even more pronounced (424+/-52 vs. 345+/-65 fpm, P<0.01). In this group, a finding of an AFR above the mean value of the study population predicted AF relapse with high accuracy. CONCLUSION: In patients undergoing cardioversion of persistent AF, AF relapse is predicted by a higher AFR. A stronger association is seen in patients with short arrhythmia duration, reflecting either rapid remodelling or pre-existing changes in those who relapse to AF.     

Impact of sinus rhythm restoration and maintenance on left ventricular function and exercise tolerance in patients with persistent atrial fibrillation

BACKGROUND: Although early improvement of haemodynamic parameters following successful cardioversion of atrial fibrillation (AF) has been well documented, the long-term benefits of sinus rhythm (SR) restoration are less obvious, mainly due to a high rate of AF relapses. AIM: To determine the impact of SR restoration and maintenance on exercise tolerance and heart failure progression in patients with persistent non-valvular AF during a one year follow-up period. METHODS AND RESULTS: We studied 104 patients (33 females, 71 males, mean age 60.4+/-7.4 years) with mild to moderate stable heart failure and persistent AF with well-controlled ventricular rate who were scheduled for cardioversion. They underwent submaximal exercise testing 24 hours before cardioversion, as well as 1 and 12 months afterwards. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol. Heart failure symptoms were assessed at the same time-points of follow-up. RESULTS: SR was presented in 66 (63.5%) patients one year after cardioversion. In patients with SR, a significant improvement in left ventricular (LV) performance, exercise capacity and heart failure symptoms was noted. There was an increase in LV fractional shortening (29.9+/-7.6% vs 35.6+/-9.3%; p<0.001), maximal workload (4.7+/-2.3 vs 8.5+/-3.0 MET; p<0.001), exercise duration (125.3+/-115.3 vs 294.7+/-216.7 sec.; p<0.001), and improvement in the NYHA functional class (p<0.001). No such changes were observed in patients who had AF relapse during follow-up or in those who had unsuccessful cardioversion. CONCLUSIONS: Successful cardioversion of persistent AF resulted in a significant improvement of exercise capacity and a decrease in heart failure symptoms during one year follow-up period only in patients who maintained SR.     

Pharmacological conversion of persistent atrial fibrillation into sinus rhythm with oral pilsicainide: pilsicainide suppression trial for persistent atrial fibrillation II.

BACKGROUND: The present study was conducted to determine the antiarrhythmic efficacy and safety of oral pilsicainide, a class Ic antiarrhythmic drug, in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: One hundred and eight patients (mean age, 58.9 years) with AF lasting >or=48 h and or=3 weeks prior to the study enrolment or after verification of the absence of left atrial thrombi by transesophageal echocardiography. After 2 weeks of treatment, an electrocardiogram was recorded to determine whether sinus rhythm was restored. Sinus rhythm was restored in 22.4% of patients treated with pilsicainide and in 2% treated with placebo (p=0.002). Cardioversion was less likely to occur with oral pilsicainide when the AF duration exceeded 2 months or if the left atrial diameter exceeded 45 mm. There was no significant difference in the adverse cardiovascular event rate between the pilsicainide- and placebo-treated groups. One patient in the pilsicainide group developed an atrial flutter without any hemodynamic deterioration. CONCLUSION: A 2-week oral administration of pilsicainide is well tolerated and moderately effective in converting persistent AF into sinus rhythm.     

Effects of sinus rhythm restoration in patients with persistent atrial fibrillation: a clinical, echocardiographic and hormonal study

The hemodynamic consequences of atrial fibrillation (AF) may lead to impairment of the left ventricular function and a reduction in exercise capacity. Studies on mechanical and neurohormonal remodelling in patients with AF are becoming increasingly important. The results could possibly enhance treatment strategies of these patients. The aim of this study was to assess changes in exercise capacity, echocardiographic findings and plasma atrial natriuretic peptide (ANP) concentrations in patients with non-rheumatic persistent AF, before and 30 days after successful cardioversion. METHODS: We attempted cardioversion in 42 consecutive patients, aged 58 +/- 8 years, with persistent non-valvular AF of duration 7.1 +/- 7.1 months. They underwent echocardiography examination and submaximal exercise testing 24 h before and 30 days after cardioversion. Exercise capacity was determined during symptom-limited exercise testing, according to a modified Bruce protocol with peak VO2 analysis. Plasma samples of ANP were obtained at rest: before, the day after, and 30 days after cardioversion therapy, and were prepared by refrigerated centrifugation and stored until radioimmunoassay. The control study group, without AF, comprised of 11 subjects. RESULTS: Cardioversion was successful in 35 patients. However, in six of the 35 patients, AF reappeared within 1 month. There were no statistical differences before cardioversion in exercise tolerance and ejection fraction of left ventricle between the group with successful cardioversion and the group with unsuccessful cardioversion or with recurrence of AF. On the 30th day after cardioversion we recorded a significant increase in exercise tolerance: duration of exercise 13.7 +/- 3.2 versus 9.5 +/- 3.4 min, (P < 0.05); peak oxygen consumption 32.2 +/- 3.6 versus 19.85 +/- 3.5 ml/min per kg, (P < 0.05); and ejection fraction of left ventricle 58.6 +/- 9.4 versus 52.7 +/- 10.2% (P < 0.05); in the sinus rhythm group. There was no significant improvement observed in the AF group. The mean baseline ANP level was 58.5 +/- 15.7 pg/ml in the study group and 34.3 +/- 10.2 pg/ml in the control group (P < 0.01). The successful therapy reduced significantly the pretreatment mean plasma ANP concentration from 58.5 +/- 15.7 to 31.4 +/- 15.0 pg/ml, (P < 0.01); the day after cardioversion, in the group of 35 patients. It remained stable for the next 30 days (36.9 +/- 15.2 pg/ml) in the group of 29 patients who remained in sinus rhythm, and increased to 53.4 +/- 16.4 pg/ml in the group of six patients who had recurrence of AF. Plasma ANP did not change in the group of seven patients with unsuccessful cardioversion. CONCLUSIONS: The restoration of sinus rhythm in patients with persistent AF was associated with a significant improvement in cardiac performance and exercise tolerance 1 month after cardioversion. Such improvement was not observed in the group with unsuccessful cardioversion or with AF recurrence. The plasma ANP concentration in patients with AF was significantly reduced after successful cardioversion and remained stable for a period of 30 days.     

Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm

The aim of this study was to investigate the efficacy and safety of bepridil (a multichannel blocker including several potassium channels) for conversion of long-lasting atrial fibrillation (AF). Bepridil restored sinus rhythm alone or in combination with aprindine in 69% of 32 patients with persistent AF lasting > or = 3 months. The time to conversion after starting bepridil was 30 +/- 12 days. An increase in fibrillation cycle length with bepridil was greater in responders (31 +/- 10%), but an increase in QTc did not differ between responders and nonresponders. Bepridil is effective and safe for terminating long-lasting persistent AF.     

Impact of rate versus rhythm control on quality of life in patients with persistent atrial fibrillation. Results from a prospective randomized study.

AIMS: Despite the high prevalence of atrial fibrillation (AF), there are only limited data on quality of life (QoL) stemming from prospective trials comparing rate versus rhythm control. This prospective study evaluated QoL in patients with symptomatic persistent AF randomized to therapy aiming at rate versus rhythm control. METHODS AND RESULTS: Patients with symptomatic persistent AF (7 to 360 days duration) were prospectively randomized to ventricular rate control (n=125) or to cardioversion and maintenance of sinus rhythm (n=127). QoL was assessed by the Medical Outcomes Study Short Form health survey (SF-36) at baseline and during 1 year of follow-up. Changes in QoL were compared on an intent-to-treat basis, and subsequently between patients in sinus rhythm versus AF. At baseline, all SF-36 scales were reduced compared to healthy controls. At 1 year, six of eight items had improved significantly in patients assigned to rate control, and five of eight items on rhythm control (p=ns). The physical component summary showed a comparable increase with both treatment strategies (rate control: p=0.004; rhythm control: p<0.001) whereas no significant changes were found for the mental component summary. At 1 year, 55% of patients reported a positive health transition with no inter-group differences. There were no significant differences in QoL in patients in sinus rhythm or AF at the end of the observation period. CONCLUSION: In patients with symptomatic persistent AF, the two treatment strategies of rate versus rhythm control are associated with similar improvements in QoL.     

Maintaining stability of sinus rhythm in atrial fibrillation: Antiarrhythmic drugs versus ablation

In managing atrial fibrillation, the main therapeutic strategies include rate control, termination of the arrhythmia, and pr vention of recurrences and thromboembolic events. Rate control with digoxin, β-blockers, verapamil, and diltiazem may be preferred in drug refractory and sedentary patients with markedly dilated left atrium and atrial fibrillation of long duration. Drugs useful in the maintenance of sinus rhythm include quinidine, procainamide, disopyramide, sotalol, amiodarone, dofetilide, flecainide, and propafenone. In patients with structural heart disease, the class III antiarrhythmics are the initial drugs of choice, given their neutral effects on survival in a post-myocardial infarction and congestive heart failure population. Due to high recurrence rates with pharmacologic therapy, nonpharmacologic options of therapy include atrioventricular junction ablation, atrial defibrillators, catheter ablation of pulmonary vein foci, and attempts to perform an atrial Maze procedure using catheters. Hybrid therapy using drugs in combination with nonpharmacologic approaches will be used more frequently in the future for refractory patients.     

Delayed improvement in exercise capacity after cardioversion of atrial fibrillation to sinus rhythm.

In some patients symptoms improve after the restoration of sinus rhythm from atrial fibrillation. To assess the size and mechanism of such change, exercise capacity and pulsed Doppler left ventricular inflow velocities were assessed in 20 patients with established atrial fibrillation. Treadmill exercise capacity was assessed by measuring maximal oxygen consumption and anaerobic threshold before and on day 1 and 28 days after elective DC cardioversion. The relative contribution of atrial contraction to left ventricular filling was determined by relating the maximum height of the A wave to the maximum height of the E wave (A/E) of the Doppler velocity time curve. Cardioversion was successful in 14 patients. Maximal oxygen consumption and anaerobic threshold were unchanged on day 1 and increased by day 28 in all 14 patients. The percentage improvement was inversely related to the baseline values; however, the absolute improvement was small in all patients. The mean A/E ratio increased significantly from day 1 to day 28 in all 14 patients. Thus the restoration of sinus rhythm was associated with a delayed improvement in exercise capacity that may in part be due to a slow improvement in atrial contractility and peak cardiac output after cardioversion.     

Restoring sinus rhythm results in blood pressure reduction in patients with persistent atrial fibrillation and a history of hypertension

Effects of Rhythm Control on Blood Pressure . Introduction: The long‐term effects of atrial fibrillation (AF) on blood pressure (BP) in patients with hypertension (HTN) remain unclear. We hypothesized that restoration of normal sinus rhythm (NSR) results in a decrease in BP despite the expected increase in cardiac output. Methods and Results: Twenty‐four‐hour BP measurements were obtained during AF, and on Day 1 and Day 30 post‐successful cardioversion in 18 patients with AF and HTN (cardioversion group), and another 22 patients with AF and HTN with no immediate plans for cardioversion (control group). Except for the duration of AF, the clinical characteristics and use of medications were similar between the groups. In the cardioversion group, a significant decrease in diastolic blood pressure (DBP) and mean blood pressure (MBP) were noted on Day 1 post‐cardioversion with no significant change in systolic blood pressure (SBP): 117/74/88 ± 13/9/9 mmHg during AF and 116/70/85 ± 13/9/10 mmHg during Day 1 post‐cardioversion (P = 0.68; <0.01 and 0.04 for SBP, DBP, and MBP, respectively). In the 13 subjects who remained in NSR at Day 30, DBP and MBP decreased further on Day 30 when compared to Day 1 with no significant change in SBP: 118/76/90 ± 13/7/8 mmHg during AF; 119/72/88 ± 12/8/9 mmHg during Day 1; and 118/69/86 ± 10/8/7 mmHg during Day 30 post‐cardioversion (P = 0.97; <0.001 and 0.03 for SBP, DBP, and MBP, respectively). In the control group, no significant changes in BP were noted. Conclusion: Restoring NSR in patients with AF and HTN resulted in a sustained decrease in DBP and MBP. To our knowledge, this is the first study to show that maintenance of NSR improves BP control in patients with AF and HTN. (J Cardiovasc Electrophysiol, Vol. 23, pp. 722‐726, July 2012)     

Propafenone versus procainamide for conversion of atrial fibrillation to sinus rhythm

Background and hypothesis: Antiarrhythmic drugs are widely used for treatment of atrial fibrillation (AF) and restoration off sinus rhythm. This prospective, randomized, and controlled study compared the efficiency and safety of propafenone versus procainamide for the treatment of acute AF. Methods: In all, 117 patients (55 women, 62 men, mean age 64.2 ± 13 years, median 63 years) who presented with AF were included in the study. Exclusion criteria were signs or symptoms of heart failure on physical examination, recent myocardial infarction or cardiac surgery, cardiogenic shock, or hypotension. Forty-one patients spontaneously recovered sinus rhythm; the remaining 76 patients were randomized to receive propafenone or procainamide. Propafenone was given at a dose of 2 mg/kg body weight intravenously (IV) over 30 min. Patients randomized to receive procainamide received a bolus of 100 mg IV administered every 5 min up to a maximum dose of 1 g. The clinical characteristics of the two groups were comparable. Results: The number of patients who recovered sinus rhythm after the treatment was larger in the procainamide-treated group (Group 1) (69.5%) than in the propafenone-treated group (Group 2) (48.7%); p < 0.05. The time required for cardioversion was significantly lower in Group 1 (mean 4.1 ± 1.3 h). than in Group 2 patients (mean 7.3 ± 2.6 h) (p<0.01). Conclusion: In the present study, procainamide was more effective than propafenone for the treatment of AF of short duration.     

Restoring sinus rhythm improves excessive heart rate response to exercise in patients with atrial fibrillation

The aim of this study was to investigate improvement in the cardiovascular response to isometric and isotonic exercises after reverting rhythm to sinus in patients with atrial fibrillation. Twenty seven cases with nonvalvular paroxysmal atrial fibrillation were included in the study. Sinus rhythm could not be restored in two cases so they were excluded. The remaining cases were divided into two groups according to the existence of cardiac diseasc. Group 1 (n:14, mean age. 60.8 +/- 14.9 years) included cases with cardiac diseases (8 of the patients had hypertension in addition to the cardiac disease) and group 2 (n:11, mean age. 64.8 +/- 13.9 years) included those without cardiac disease (patients with hypertension and diabetes mellitus). Isometric and isotonic exercise tests were performed in all of the patients before and 48 hours after the rhythm was reverted to sinus and the values in atrial fibrillation were compared with those in sinus rhythm (following cardioversion). The isotonic exercise period increased significantly in only group 1 patients following cardioversion (P = (0.0061). In both groups, the increase in heart rate during atrial fibrillation was significantly higher compared to those after being reverted to sinus, at all stages of the isotonic exercise (in groups 1 and 2, heart rate in patients with atrial fibrillation increased from 96.5 +/- 19.3 to 173.3 +/- 19.3 beats/min and 96.1 +/- 12.6 to 185.0 +/- 12.1 beats/ min, respectively; and in sinus rhythm, it ranged from 85.1 +/- 11.4 to 164.6 +/- 9.1 beats/min and 81.3 +/- 11.4 to 157.6 +/- 15.1 beats/min, respectively). Systolic arterial pressure increased significantly during atrial fibrillation in group 1, at the 2nd stage of the isotonic exercise test (P = 0.0070). In group 2, systolic arterial pressure increased significantly at the 3rd stage in sinus rhythm and at the 4th stage when in rhythm in atrial fibrillation. Also, diastolic arterial pressure increased significantly during atrial fibrillation only at the 3rd stage of the exercise. As a result, restoring sinus rhythm by cardioversion improves excessive heart rate responses to exercise significantly in patients with atrial fibrillation during both isometric and isotonic exercises. Also, we have revealed that the exercise time increased significantly by restoring sinus rhythm in patients with heart disease.     

Flecainide versus quinidine for conversion of atrial fibrillation to sinus rhythm

The effectiveness and safety of flecainide and quinidine for conversion of atrial fibrillation (AF) to sinus rhythm were compared. Sixty consecutive patients were treated with either flecainide (up to 2 mg/kg intravenously and then orally) or quinidine (up to 1.2 g orally). There was no statistical difference in age, left atrial size, duration of the arrhythmia and underlying cardiac diseases between the 2 groups. The overall conversion rate to sinus rhythm was 63% (38 patients): AF was converted in 18 patients (60%) treated with quinidine and 20 (67%) with flecainide. If AF lasted less than 10 days, the conversion rate was 86% in the flecainide group and 80% in the quinidine group (difference not significant). When AF lasted more than 10 days the rate was 22% in the flecainide group and 40% in the quinidine group. Adverse effects were more frequent in the quinidine group (27%) (gastrointestinal disturbances) than in the flecainide group (7%) (conduction disturbances), but they were less severe in the quinidine group. Thus, flecainide given intravenously appeared to be as effective as quinidine given orally for conversion of AF of recent onset (within 10 days). However, quinidine should probably remain the preferred drug for conversion of AF of long duration (more than 10 days) to sinus rhythm. Adverse effects occurred less often with flecainide therapy, but they were more severe.