The effectiveness and safety of d,l-sotalol in the ambulatory treatment of atrial fibrillation and flutter]

Data on short and long term efficacy and safety of d,l sotalol in patients with atrial fibrillation or atrial flutter is limited. The aims of this study were to (1) assess the antiarrhythmic efficacy of d,l sotalol maintaining normal sinus rhythm in patients with refractory atrial fibrillation or flutter, (2) evaluate the efficacy of d,l sotalol in preventing recurrences of paroxysmal atrial fibrillation or flutter, (3) evaluate the control of ventricular rate in patients with paroxysmal or refractory atrial fibrillation or flutter unsuccessfully treated with other antiarrhythmic agents, (4) determine predictors of efficacy (5) assess the safety of d,l sotalol in this setting. Two hundred patients with chronic or paroxysmal atrial fibrillation or atrial flutter or both, who had failed one to six previous antiarrhythmic drug trials were treated with d,l sotalol 80 to 440 mg/day orally. Fifty four percent was female, age 47 +/- 16 years (range 7-79), follow up period 7 +/- 7 months (range 1 to 14 months), 79% of patients had the arrhythmia for more than one year. The atrial fibrillation in 37.5% of patients was chronic and paroxysmal in 23.5. The atrial flutter was chronic in 31% of patients and paroxysmal in 8%. Eighty two percent of patients was in functional class I (NYHA) and 82% had cardiac heart disease: left atrial (LA) size 44 +/- 10 mm, right atrial (RA) size 37 +/- 7 mm and left ventricular ejection fraction (LVEF) 58 +/- 8%. Total success was achieved in 58% of patients (atrial fibrillation 40% and 18% in atrial flutter), partial success in 38% (atrial fibrillation in 18% and 20% in atrial flutter) and 4% of patients failure. It was p < 0.07 when compared total success vs partial success among atrial fibrillation and atrial flutter groups. Patients with cardiac heart disease responded worst (p = 0.10) to the drug than those without it, specially if the heart was dilated. We concluded that d,l sotalol has moderate efficacy to convert and maintain normal sinus rhythm, as well as it acts controlling paroxysmal relapses and ventricular heart rate.     

A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation

STUDY OBJECTIVE: A prospective, randomized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone (active treatment) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours. METHODS: We prospectively randomly assigned 120 patients with atrial fibrillation of less than 24 hours' duration to treatment with sotalol, amiodarone, or digoxin using a single intravenous dose followed by 48 hours of oral treatment. Patients had ECG monitoring for 48 hours, and time of reversion, adequacy of rate control, and numbers of adverse events were compared. After 48 hours, those still in atrial fibrillation underwent cardioversion according to a standardized protocol. After 48 hours of therapy and attempted cardioversion, the number of patients whose rhythms had successfully reverted were compared. RESULTS: There was a significant reduction in the time to reversion with both sotalol (13. 0+/-2.5 hours, P <.01) and amiodarone (18.1+/-2.9 hours, P <.05) treatment compared with digoxin only (26.9+/-3.4 hours). By 48 hours, the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group (95% versus 78%, P <.05; risk ratio 5.4, 95% confidence interval [CI] 1.5 to 19.2 ). In those patients whose rhythms did not revert to sinus rhythm, there was superior ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin. There were also fewer adverse events in the active treatment group compared with the rate control group. CONCLUSION: Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs (sotalol or amiodarone) improves complication-free 48-hour reversion rates compared with rate control with digoxin.     

Effect of low dose sotalol on the signal averaged P wave in patients with paroxysmal atrial fibrillation.

OBJECTIVE--To investigate the effects of low dose sotalol on the signal averaged surface P wave in patients with paroxysmal atrial fibrillation. DESIGN--A longitudinal within patient crossover study. SETTING--Cardiac departments of a regional cardiothoracic centre and a district general hospital. PATIENTS--Sixteen patients with documented paroxysmal atrial fibrillation. The median (range) age of the patients was 65.5 (36-70) years; 11 were men. MAIN OUTCOME MEASURES--Analysis of the signal averaged P wave recorded from patients not receiving antiarrhythmic medication and after 4-6 weeks'' treatment with sotalol. P wave limits were defined automatically by a computer algorithm. Filtered P wave duration and energies contained in frequency bands from 20, 30, 40, 60, and 80 to 150 Hz of the P wave spectrum expressed as absolute values (P20, P30, etc) and as ratios of high to low frequency energy (PR20, PR30, etc) were measured. RESULTS--No difference in P wave duration was observed between the groups studied (mean (SEM) 149 (4) without medication and 152 (3) ms with sotalol). Significant decreases in high frequency P wave energy (for example P60: 4.3 (0.4) v 3.3 (0.3) microV2.s, P = 0.003) and energy ratio (PR60: 5.6 (0.5) v 4.7 (0.6), P = 0.03) were observed during sotalol treatment. These changes were independent of heart rate. CONCLUSIONS--Treatment with low dose sotalol reduces high frequency P wave energy but does not change P wave duration. These results are consistent with the class III effect of the drug and suggest that signal averaging of the surface P wave may be a useful non-invasive measure of drug induced changes in atrial electrophysiology.     

Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators

OBJECTIVES: The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both. BACKGROUND: Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem. METHODS: A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test. RESULTS: In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002). CONCLUSIONS: Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.     

Atrial Fibrillation and Hypercoagulability: Dependent on Clinical Factors or/and on Genetic Alterations?

It is well known that atrial fibrillation is associated with high incidence of thromboembolic events, propably due to a prothrombotic or hypercoagulable state. However, it is unclear whether or not there is any difference of this prothrombotic state in the clinical subgroups of atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. From the other side the role of the arrhythmia duration on the changes of coagulative variables in atrial fibrillation patients is not clearly enough.The contribution of genetic and functional alterations in factors of the coagulation and fibrinolytic pathways (that is hemostatic risk factors) to the development of hypercoagulation state in atrial fibrillation requires clarification. We investigated therefore (1) if there are differences in the prothrombotic state between patients with different clinical status of the arrhythmia, (2) if the arrhythmia duration per se could be an independent determinant of the prothrombotic state in all atrial fibrillation patients and (3) if coexistent genetic alterations in haemostatic risk factors in patients with atrial fibrillation could contribute to the development of prothrombotic abnormalities. METHODS: Over a period of 23 months, we studied 55 patients with chronic non-valvular atrial fibrillation. We recruited 18 consecutive patients (13 men, mean age 59 +/- 10 years) with paroxysmal atrial fibrillation 17 patients (11 men, mean age 61 +/- 7 years) with persistent atrial fibrillation who underwent elective successful DC and remained in sinus rhythm at the 3 month visit and 20 patients (14 men mean age 64 +/- 9) with permanent atrial fibrillation. Blood results were compared to 17 age-sex- and race-matched controls. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P -selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). We assessed the frequencies of factor V Leiden and prothrombin variant G20210A to determine whether particular inherited haemostatic risk factors may have contribution to the development of prothrombotic state in atrial fibrillation patients. RESULTS: Permanent atrial fibrillation was associated with significant raised levels of von Willebrand factor, fibrinogen levels and soluble P -selectin compared to matched controls (all p < 0.001) and matched patients with paroxysmal and permanent AF (all p ranged between <0.003 and <0.002). Patients with persistent atrial fibrillation had significantly elevated von Willebrand factor levels (p = 0.0064) and fibrinogen levels (p = 0.002), but not Soluble P -selectin (p = 0.509). when compared to controls. Patients with paroxysmal atrial fibrillation had significantly elevated levels of P -selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p =.0.61) compared to controls. Stepwise multiple regression analyses demonstrated that the arrhythmia duration (approximately 3 years) was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P -selectin levels. Restoration of sinus rhythm in paroxysmal atrial fibrillation subgroup and successful electrical cardioversion of patients with permanent fibrillation atrial fibrillation did not significantly alter levels of the affected factors. The frequency of factor V Leiden was 8.9 in all studied patients with atrial fibrillation, versus 2.4% in the control group (odds ratio [OR] 4.6 [95% confidence (CI) 1.4-17.5], p = 0.02). The frequency of the prothrombin variant G20210A was 6.4.% compared with control group 1.6% (OR 4.9 [95% confidence interval (CI) 1.2-2.9], p = 0.04).There was a trend towards an increased frequency of factor V Leiden and/or prothrombin variant G20210A in patients age <55 years and in patients living at a particular area of Thrace mountains. CONCLUSIONS: Our results showed that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched patients with permanent atrial fibrillation and controls in sinus rhythm.The duration of the arrhythmia (about 3 years) was an independent predictor of abnormal measured factors. We found for the first time that some genetic alterations in haemostatic risk factors could be coexist in atrial fibrillation patients and may be a contributor to the development of hypercoagulability in atrial fibrillation patients.     

Comparison of effects of nebivolol and atenolol on P-wave dispersion in patients with hypertension

BACKGROUND: P-wave dispersion has been shown to be a noninvasive electrocardiographic predictor for development of atrial fibrillation . Thus it may be possible to attenuate atrial fibrillation risk through normalization of P-wave variables and improvement in P-wave dispersion may be an important goal in treatment of hypertension. OBJECTIVE: To compare the effects of nebivolol, a new b-blocker that have additional vasodilating activity via acting on endothelium and nitric oxide release, and atenolol on P-wave duration and dispersion in patients with mild-to-moderate hypertension. METHODS: A total of 34 newly-diagnosed hypertensive patients were enrolled in the study. The patients were randomly assigned to receive treatment with either nebivolol (5 mg) or atenolol (50 mg). P-wave durations (Pmin and Pmax) and P-wave dispersion were measured before and one month after treatment. RESULTS: While Pmin increased (50,6 +/- 11,2 ms to 54,7 +/- 9,1 ms, p=0,05), Pmax decreased (111,9 +/- 9,1 ms to 104,0 +/- 12,4 ms, p=0,003) and P-wave dispersion decreased (62,5 +/- 10,6 ms to 51,3 +/- 8,9 ms, p < 0,001) with nebivolol, Pmin increased (44,4 +/- 9,8 ms to 58,0 +/- 15,5 ms, p=0,02), Pmax didn t change (106,1 +/- 13,8 ms to 107,0 +/- 11,6 ms, p=NS) and P-wave dispersion decreased (61,7 +/- 15,0 ms to 49,0 +/- 13,7 ms, p < 0.001) with atenolol. However, there was no statistical difference between pre- and post-treatment values of two groups. CONCLUSIONS: Both nebivolol and atenolol are effective in improvement of P-wave dispersion in patients with hypertension and there s no significant difference between them.     

药物治疗高龄患者阵发性心房颤动的1年随访

目的 观察胺碘酮、普罗帕酮、索他洛尔治疗老年阵发性心房颤动的疗效.方法 82例年龄85岁及以上高龄的阵发性心房颤动患者随机分为胺碘酮组 （39例）、普罗帕酮组 （21例） 和索他洛尔 （22 例） 组,分别选用胺碘酮、普罗帕酮、索他洛尔进行复律治疗.结果 3组患者服药后48h内有效率分别为 96%、35%、17%,组间差异有统计学意义.1年随访有效率分别为 86%、25%、1l%,组间差异有统计学意义.3组药物的不良反应发生率分别为 26%、15%、10%,差异有统计学意义;胺碘酮严重不良反应多见.结论 3种药物中胺碘酮治疗高龄患者阵发性心房颤动的疗效最佳,但不良反应明显,其他两种药物有一定疗效,但不良反应相对较少.     

Azimilide vs. placebo and sotalol for persistent atrial fibrillation: the A-COMET-II (Azimilide-CardiOversion MaintEnance Trial-II) trial.

AIMS: Treatment of atrial fibrillation remains a major clinical challenge owing to the limited efficacy and safety of anti-arrhythmic drugs, particularly in patients with structural heart disease. METHODS AND RESULTS: To evaluate the efficacy of azimilide, a new class III anti-arrhythmic drug, we studied 658 patients with symptomatic persistent atrial fibrillation, adequate anticoagulant therapy, and planned electrical cardioversion. Patients were randomized to placebo, azimilide (125 mg o.d.), or sotalol (160 mg b.i.d.). Primary efficacy analysis was based on event recurrence, which was defined as atrial fibrillation lasting>24 h, or requiring DC cardioversion. Median time to recurrence was 14 days for azimilide, 12 days for placebo, and 28 days for sotalol (P=0.0320 when comparing azimilide with placebo; P=0.0002 when comparing azimilide with sotalol). The placebo-to-azimilide hazard ratio was 1.291 (95% CI: 1.022-1.629) and the sotalol-to-azimilide hazard ratio was 0.652 (95% CI: 0.523-0.814). Adverse events causing patient withdrawal were more frequent (P<0.01) in patients on azimilide (12.3%) and on sotalol (13.9%) than on placebo (5.4%). Eight patients in the sotalol (3.5%) and 16 in the azimilide (7.6%) group interrupted the study because of QTc prolongation. Torsade de pointes was reported in five patients of the azimilide group. The percentage of patients who completed the 26 week study period without events were 19% for azimilide, 15% for placebo, and 33% for sotalol (P<0.01). Unsuccessful day 4 cardioversion, arrhythmia recurrence, and adverse events were the main causes of withdrawal from the study. CONCLUSION: This study demonstrates that the anti-arrhythmic efficacy of azimilide is slightly superior to placebo but significantly inferior to sotalol in patients with persistent AF. The modest anti-arrhythmic efficacy and high rate of torsade de pointes and marked QTc prolongation limit azimilide utilization for the treatment of AF.     

T wave alternans after sotalol: evidence for increased sensitivity to sotalol after conversion from atrial fibrillation to sinus rhythm

A 64 year old woman with an 11 year history of paroxysmal atrial fibrillation presented to the emergency room because of palpitations that had started two weeks previously. She had used sotalol 80 mg once daily for three years without any episodes of proarrhythmia or other adverse effects. However, she developed pronounced T wave alternans with giant inverted T waves and excessive QT prolongation following sotalol administration one day after conversion from atrial fibrillation to sinus rhythm. This case demonstrates bizarre T wave changes, T wave alternans, and extreme QT prolongation following sotalol administration shortly after conversion from atrial fibrillation to sinus rhythm. In this situation, sotalol administration may be proarrhythmic, because it enhances repolarisation inhomogeneities based on a spatially inhomogeneous distribution of repolarisation controlling ion channels to induce repolarisation abnormalities that may lead to torsade de pointes.

Keywords: T wave alternans; long QT syndrome; torsade de pointes; sotalol; atrial fibrillation     

Atrial Fibrillation Ablation by Use of Electroanatomical Mapping: Efficacy and Recurrence Factors

Background

Radiofrequency catheter ablation guided by electroanatomical mapping is currently an important therapeutic option for the treatment of atrial fibrillation. The complexity of the procedure, the several techniques used and the diversity of the patients hinder the reproduction of the results and the indication for the procedure.

Objective

To evaluate the efficacy and factors associated with recurrence of atrial fibrillation.

Methods

Prospective cohort study with consecutive patients submitted to atrial fibrillation ablation treatment guided by electroanatomical mapping. The inclusion criteria were as follows: minimum age of 18 years; presence of paroxysmal, persistent or long-standing persistent AF; AF recording on an electrocardiogram, exercise testing or Holter monitoring (duration longer than 15 minutes); presence of symptoms associated with AF episodes; AF refractoriness to, at least, two antiarrhythmic drugs, one of which being amiodarone, or impossibility to use antiarrhythmic drugs.

Results

The study included 95 patients (age 55 ± 12 years, 84% men, mean CHADS2 = 0.8) who underwent 102 procedures with a median follow-up of 13.4 months. The recurrence-free rate after the procedure was 75.5% after 12 months. Atrial fibrillation recurred as follows: 26.9% of patients with paroxysmal and persistent atrial fibrillation; 45.8% of patients with long-standing persistent atrial fibrillation (p = 0.04). Of the analyzed variables, the increased size of the left atrium has proven to be an independent predictor of atrial fibrillation recurrence after the procedure (HR = 2.58; 95% CI: 1.26-4.89). Complications occurred in 4.9% of the procedures.

Conclusion

Atrial fibrillation ablation guided by electroanatomical mapping has shown good efficacy. The increase in left atrium size was associated with atrial fibrillation recurrence.     

Postoperative treatment with carvedilol, a beta-adrenergic blocker, prevents paroxysmal atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Arrhythmias following cardiovascular surgery lead to unstable hemodynamics, along with myocardial ischemia and decreased cardiac output. The purpose of the present case cohort study compared the control group with no carvedilol administered and the other group of patients given carvedilol and determined whether postoperative treatment with carvedilol, a beta-adrenergic blocker, prevents paroxysmal atrial fibrillation after coronary artery bypass grafting (CABG). METHODS AND RESULTS: Of 160 patients who underwent scheduled isolated CABG, 80 received postoperative carvedilol and 80 did not. Postoperative paroxysmal atrial fibrillation was defined as episodes of atrial fibrillation persisting for over 10 min and confirmed by 12-lead electrocardiography. The incidence of paroxysmal atrial fibrillation was significantly lower in patients given carvedilol (12/80:15%) than in those who were not (27/80:34%) (p=0.0094). Logistic regression analysis showed that only postoperative carvedilol was significantly associated with the development of postoperative atrial fibrillation (95% confidence interval, 0.169-0.832; p=0.0159). CONCLUSION: Postoperative treatment with carvedilol prevented paroxysmal atrial fibrillation after CABG.     

Oral d,l sotalol reduces the incidence of postoperative atrial fibrillation in coronary artery bypass surgery patients: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The purpose of this prospective, randomized, double-blind, placebo-controlled study was to assess the efficacy of preoperatively and postoperatively administered oral d,l sotalol in preventing the occurrence of postoperative atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is the most common arrhythmia following coronary artery bypass surgery (CABG). Its etiology, prevention and treatment remain highly controversial. Furthermore, its associated morbidity results in a prolongation of the length of hospital stay post-CABG. METHODS: A total of 85 patients, of which 73 were to undergo CABG and 12 CABG plus valvular surgery (ejection fraction > or = 28% and absence of clinical heart failure), were randomized to receive either sotalol (40 patients; mean dose = 190 +/- 43 mg/day) started 24 to 48 h before open heart surgery and continued for four days postoperatively, or placebo (45 patients, mean dose = 176 +/- 32 mg/day). RESULTS: Atrial fibrillation occurred in a total of 22/85 (26%) patients. The incidence of postoperative AF was significantly (p = 0.008) lower in patients on sotalol (12.5%) as compared with placebo (38%). Significant bradycardia/hypotension, necessitating drug withdrawal, occurred in 2 of 40 (5%) patients on sotalol and none in the placebo group (p = 0.2). None of the patients on sotalol developed Torsade de pointes or sustained ventricular arrhythmias. Postoperative mortality was not significantly different in sotalol versus placebo (0% vs. 2%, p = 1.0). Patients in the sotalol group had a nonsignificantly shorter length of hospital stay as compared with placebo (7 +/- 2 days vs. 8 +/- 4 days; p = 0.24). CONCLUSIONS: The administration of sotalol, in dosages ranging from 80 to 120 mg, was associated with a significant decrease (67%) in postoperative AF in patients undergoing CABG without appreciable side effects. Sotalol should be considered for the prevention of postoperative AF in patients undergoing CABG in the absence of heart failure and significant left ventricular dysfunction.     

Cardiovascular morbidity and mortality in hypertensive patients with lower versus higher risk: a LIFE substudy

We hypothesized that losartan was superior to atenolol in reducing cardiovascular events in a lower-risk group (LRG) versus a higher-risk group (HRG) of patients in a Losartan Intervention For Endpoint reduction (LIFE) substudy, independently of blood pressure (BP) reduction. In a post hoc analysis, we designated 4282 patients as LRG on the basis of: (1) no previous cardiovascular disease (coronary, cerebral, peripheral vascular disease); (2) no diabetes; (3) no isolated systolic hypertension; and (4) inclusion of the lowest 3 quartiles of electrocardiographically documented left ventricular hypertrophy. The HRG consisted of 4911 remaining patients who did not qualify for the LRG. In the LRG, losartan was superior to atenolol in reducing stroke: hazard ratio (HR), 0.72 (95% confidence interval [CI], 0.53 to 0.98); new-onset diabetes (HR, 0.74 [95% CI, 0.58 to 0.93]; and new-onset atrial fibrillation: HR, 0.69 (95% CI, 0.51 to 0.92), all P<0.05 but not composite end points or cardiovascular mortality (both P=NS). In the HRG, losartan was superior to atenolol in reducing composite end points: HR, 0.82 (95% CI, 0.71 to 0.94), P<0.01; cardiovascular mortality: HR, 0.77 (95% CI, 0.62 to 0.95), P<0.05; stroke: HR, 0.75 (95% CI, 0.61 to 0.92), P<0.01; new-onset diabetes: HR, 0.76 (95% CI, 0.60 to 0.96), P<0.05; and new-onset atrial fibrillation: HR, 0.71 (95% CI, 0.58 to 88), P<0.05. Test for interaction of treatment with LRG versus HRG was not significant for composite end point, stroke, or atrial fibrillation, but was for cardiovascular mortality (P=0.018). Achieved systolic BP reduction favored losartan over atenolol by -1.8 mm Hg in LRG (P=NS) and -0.7 mm Hg (P=0.001) in HRG, but no significant differences occurred in diastolic or mean BP in either group. In conclusion, losartan compared with atenolol reduces the risk of stroke, new-onset diabetes, and new-onset atrial fibrillation in the LRG and the HRG.     

Predictors of non-pharmacological intervention in patients with paroxysmal atrial fibrillation: Value of neuroticism

BACKGROUND: Non-pharmacological intervention is gaining increasing popularity in the treatment of patients with paroxysmal atrial fibrillation. We sought to investigate which factors play a role in the choice for non-pharmacological intervention with a particular focus on neuroticism. METHODS: The study group comprised 73 patients with paroxysmal atrial fibrillation (mean age 55+/-13 years, 50 males). On average, patients had a 3-year-history of one symptomatic paroxysm per week lasting 2 h. The degree of neuroticism was assessed using the short scale Eysenck Personality Questionnaire. RESULTS: During a mean follow-up period of 7.0+/-0.6 years, 20 patients (27%) underwent a non-pharmacological intervention for atrial fibrillation including His bundle ablation (n = 1), maze operation (n = 4), DDDR-pacemaker (n = 10), pulmonary vein ablation (n = 5). Multivariate regression analysis showed that age < 55 years (odds ratio 5.3, 95% CI 1.1-24.5), frequency of paroxysms of atrial fibrillation > 1 per week (odds ratio 5.9, 95% CI 1.2-28.5) and total number of anti-arrhythmic drugs (class I and III) used > 2 (odds ratio 3.4, 95% CI 1.6-6.9) were predictive of non-pharmacological intervention (all p < 0.05). In contrast, the degree of neuroticism was similar in patients who underwent non-pharmacological intervention as opposed to patients who did not undergo non-pharmacological intervention (4.5+/-3.3 vs. 4.0+/-2.9, p = NS). CONCLUSIONS: On the basis of this small study, neuroticism would not appear to play an important role in the decision to perform a non-pharmacological intervention. Instead, the data indicate that younger patients with pharmacologically refractory atrial fibrillation more often undergo non-pharmacological intervention.     

Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens

OBJECTIVESWe compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF).BACKGROUNDSystematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported.METHODSIn 12 patients (11 male, 69 ± 6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis.RESULTSThe 24-h mean (±SD) values of VR (bpm) were − digoxin: 78.9 ± 16.3, diltiazem: 80.0 ± 15.5, atenolol: 75.9 ± 11.7, digoxin + diltiazem: 67.3 ± 14.1 and digoxin + atenolol: 65.0 ± 9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns).CONCLUSIONSThis study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.     

2 year follow-up of 321 patients with an implantable cardioverter/defibrillator: comparison of patients with and without atrial fibrillation

Atrial fibrillation is the most common cause of inappropriate therapy deliveries by implantable cardioverter/defibrillators (ICD). However, the importance of atrial fibrillation for the induction of ventricular arrhythmias and for the prognosis is controversial. We studied 321 ICD patients (pts) over the median follow-up of 25 months. In 92 pts, atrial fibrillation was found to be the underlying rhythm (in 49 pts chronic, in 43 pts paroxysmal), in 229 pts sinus rhythm. Pts with atrial fibrillation were older (67 +/- 9 vs. 63 +/- 9 years, p = 0.001) and were considered to suffer more often from a valvular (14 vs. 4%, p = 0.004) or a dilative cardiomyopathy (29 vs. 19%, p = 0.04). Both groups were similar regarding other baseline characteristics like gender, left ventricular ejection fraction, hypertension, diabetes and in the ICD system (single chamber, dual chamber) used. Pts with atrial fibrillation experienced more appropriate (ventricular fibrillation: 0.33 vs. 0.2/month, p = 0.0049, ventricular tachycardias: 0.05 vs 0/month, p = 0.0033) as well as inappropriate (34 vs. 8%, p < 0.001) therapy deliveries by the ICD. Pts with atrial fibrillation were found to suffer twice as much from a progression of their heart failure (43% vs. 22%, p < 0.001). After multivariate analysis, atrial fibrillation was significantly associated with progressive pump-failure mortality (relative risk (RR) 3.12, confidence interval (CI) 1.30 to 7.48, p = 0.01). There was no difference in the incidence of ICD therapies and mortality rates between the pts with chronic and paroxysmal atrial fibrillation. CONCLUSION: The presence of atrial fibrillation in ICD patients is associated with a progression of heart failure and therefore is an unfavorable factor for pump-failure death. Also, atrial fibrillation is a marker for greater possibility to experience more appropriate as well as inappropriate therapy deliveries by the ICD.     

Risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter.

AIMS: Catheter ablation of the inferior vena cava-tricuspid annulus isthmus and continuation of antiarrhythmic drug therapy have been shown to be an effective hybrid therapy for atrial flutter which results from antiarrhythmic drug treatment of atrial fibrillation. The aim of this study was to determine the risk factors for recurrence of atrial fibrillation in patients undergoing hybrid therapy for antiarrhythmic drug-induced atrial flutter. METHODS AND RESULTS: 90 patients with paroxysmal (n=46) or persistent atrial fibrillation (n=44) developed atrial flutter due to the administration of amiodarone (n=48), flecainide (n=22), propafenone (n=14) or sotalol (n=6). Recurrence of atrial fibrillation after ablation was assessed during follow-up on continued antiarrhythmic drug therapy and during long-term follow-up, irrespective of the initial antiarrhythmic medication. During the follow-up on continued antiarrhythmic drug therapy (16+/-13 months), recurrence of atrial fibrillation was documented in 24 of 90 patients (27%). The presence of accompanying pre-ablation episodes of atrial fibrillation on antiarrhythmic treatment (Odds ratio 7.1, 95% confidence interval 2.3 to 25, p=0.001) and decreased left ventricular ejection fraction (Odds ratio 3.7, 95% confidence interval 1.01 to 12.5, p=0.048) were significant and independent predictors of post-ablation atrial fibrillation. Antiarrhythmic medication was discontinued during long-term follow-up due to adverse drug effects (amiodarone, n=12; flecainide, n=1) in 13 patients (14%). During the long-term follow-up, irrespective of the initial antiarrhythmic medication (21+/-15 months), stable sinus rhythm was maintained in 60 of 90 patients (67%). CONCLUSION Hybrid therapy can be considered as the first line therapy for patients with antiarrhythmic drug-induced atrial flutter but patients should be carefully evaluated for accompanying pre-ablation episodes of atrial fibrillation and possible adverse drug effects before initiation of hybrid therapy.     

Safety of flecainide versus propafenone for the long-term management of symptomatic paroxysmal supraventricular tachyarrhythmias: Report from the Flecainide and Propafenone Italian Study (FAPIS) group

In order to compare the long-term safety of flecainide and propafenone,an open label, randomized, parallel group study was performedin 335 patients with paroxysmal atrial fibrillation (n=200)or paroxysmal supra ventricular tachycardia (n=135), and nohistory of heart disease. Patients were treated with an initialdaily dose of flecainide 100 mg (n=72) or propafenone 450 mg(n=63) for paroxysmal supraventricular tachycardia and flecainide200 mg (n=97) or propafenone 450 mg (n=103) for paroxysmal atrialfibrillation. Dose escalations were permitted after 2 attacks,up to a maximum of flecainide 300 mg or propafenone 900 mg.day^–1. Follow-up duration was 12 months, or when patientsstopped the treatment as a result of inadequate efficacy oradverse experiences. Twelve patients on flecainide reported 16 cardiac adverse experiences,of whom six discontinued the treatment. Seven propafenone patientshad eight cardiac adverse experiences, of whom five discontinuedthe treatment. Serious proarrhythmic events were infrequent:one case of ventricular tachycardia on propafenone; two casesof atrial fibrillation with rapid ventricular response on flecainide,associated in one patient with pulmonary oedema. An intention-to-treat analysis showed that the probability of12 months' safe and effective treatment of paroxysmal supraventriculartachycardia was 93% for flecainide and 86% for propafenone (P=0·24),whereas in paroxysmal atrial fibrillation it was 77% for flecainideand 75% for propafenone (P=0·72). In conclusion, flecainide and propafenone were safe in the long-termtreatment of patients with paroxysmal supraventricular tachyarrhythmiasand without evidence of clinically significant heart disease.     

The effect of oral magnesium, alone or as an adjuvant to sotalol, after cardioversion in patients with persistent atrial fibrillation.

AIMS: To determine whether magnesium given orally decreases the recurrence rate of atrial fibrillation after elective direct current cardioversion of persistent atrial fibrillation. METHODS AND RESULTS: Consecutive outpatients were randomized to treatment with oral magnesium (10.3 mmol) or placebo twice daily in a double-blind fashion. Two groups were studied; magnesium study: 170 patients with atrial fibrillation persistent for >1 month, scheduled for their first direct current cardioversion. No concomitant antiarrhythmic drugs of class I or III were allowed. Sotalol and magnesium study: 131 patients with recurrence of persistent atrial fibrillation after previous direct current cardioversion, or a history of paroxysmal atrial fibrillation, treated with sotalol. Patients were followed until recurrence of atrial fibrillation or for at least 6 months. Magnesium study: at cardioversion 67 of 85 (79%) in the placebo group and 64 of 85 (75%) in the magnesium group had converted to sinus rhythm. At the end of the study, with a follow-up of 6 to 42 months, 15% of patients in the placebo group and 19% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.37). Sotalol and magnesium study: pharmacological conversion to sinus rhythm, after oral treatment, was achieved in 34 of 131 (26%) patients. Sinus rhythm, with or without cardioversion, was restored in 89% and 85% of the patients in the placebo and magnesium groups, respectively. At the end of the study, with a follow-up of 6 to 42 months, 37% of patients in the placebo group and 30% of patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.64). CONCLUSION: In patients with persistent atrial fibrillation, oral treatment with magnesium alone or as an adjuvant to sotalol, does not influence the recurrence rate of atrial fibrillation after elective cardioversion.     

Cardioversion with sotalol in selected patients with vagally and adrenergically mediated paroxysmal atrial fibrillation.

This study was designed to evaluate and compare the effects of oral sotalol for the treatment of vagal and adrenergic paroxysmal atrial fibrillation (PAF). Thirty-five eligible patients with atrial fibrillation of > 12 hours and < 7 days were enrolled in the study. Patients were classified as vagally mediated (group I, n: 14) and adrenergically mediated (group II, n: 21) PAF groups. All patients were given racemic sotalol at a dose up to 120 mg bid for 2 days. At the end of the observation period of 48 hours, 36% of patients (n: five) in group I returned to sinus rhythm. Conversion rate in group II was 71% (n: 15), and this figure was significantly higher than the success rate in group I. Mean times to cardioversion were 22 +/- 15 hours in group I and 16 +/- 14 hours in group II (p < 0.05). The result of this study suggests that oral sotalol is more effective for adrenergic PAF. This beneficial effect of sotalol is not apparent in vagal PAF patients.