Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.     

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study.

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.     

Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion

We evaluated the efficacy of an intravenous infusion of procainamide in 26 consecutive candidates for cardioversion of atrial fibrillation. Procainamide was administered at a rate of 15 to 20 mg/min up to a maximum of 1000 mg. The treatment was considered effective only if cardioversion occurred during the procainamide infusion. Conversion to sinus rhythm occurred in 15 patients. Converters had a significantly shorter mean duration of atrial fibrillation (6 +/- 7 days, mean +/- S.D.) compared to nonconverters (79 +/- 88 days) (p less than 0.01). The mean left atrial size of converters (4.3 +/- 0.6 cm) did not differ significantly from that of nonconverters (4.7 +/- 0.9 cm). The dose of procainamide required for cardioversion ranged from 3.6 to 16.4 mg/kg. Two patients developed nonsustained ventricular tachycardia, and there was one episode of bifascicular block during the infusion. Intravenous procainamide is an effective form of therapy for conversion of atrial fibrillation of new onset.     

Reversion of recent-onset atrial fibrillation to sinus rhythm by intravenous flecainide

Spontaneous reversion to sinus rhythm is a frequent occurrence in recent-onset atrial fibrillation (AF). In a randomized, double-blind, controlled study, intravenous flecainide (2 mg/kg, maximum dose 150 mg) was compared with placebo in the treatment of recent-onset AF (present for greater than or equal to 30 minutes and less than or equal to 72 hours' duration and a ventricular response greater than or equal to 120 beats/min). Intravenous digoxin (500 micrograms) was administered concurrently to all patients in both groups who had not previously taken digoxin. The trial medication was administered over 30 minutes. Exclusion criteria included hemodynamic instability, severe heart failure, recent antiarrhythmic therapy, hypokalemia and pacemaker dependence. One hundred two consecutive patients with recent-onset AF were enrolled in the study. All patients underwent continuous electrocardiographic monitoring in the intensive care or coronary care unit. Twenty-nine (57%) patients given flecainide and digoxin, but only 7 (14%) given placebo and digoxin, reverted to sinus rhythm in less than or equal to 1 hour after starting the trial medication infusion and remained in stable sinus rhythm (chi-square 18.9, p = 0.000013; odds ratio 8.3, 95% confidence interval 2.9 to 24.8). At the end of the 6-hour monitoring period, 34 patients (67%) in the flecainide-digoxin group were in stable sinus rhythm, whereas only 18 patients (35%) in the placebo-digoxin group had reverted (chi-square 8.83, p = 0.003; odds ratio 3.67, 95% confidence interval 1.5 to 9.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

阵发性房颤自行转复的预测性

目的 发现预测房颤病人自行转复的相关因素,并初步探讨其临床意义.方法 采用Logistic回归分析法分析和比较1988年9月至1998年9月我院收治的192例发病时间＜72 h的房颤自行转复和非自行转复病人的临床特点和超声心动检查结果.结果 入院时房颤持续时间＜24 h的自行转复病人和非自行转复病人分别为118例(89.4%)和40例(66.7%).结论 房颤发作时间＜24 h是房颤自行转复的唯一预测指标.对自行转复可能性大的病人,可延缓使用转复心律的药物和直流电转复.     

Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo

AIMS: A randomized, double-blind study with a high dose of digoxinadministered intravenously for conversion of atrial fibrillation(not due to haemodynamic alterations) to sinus rhythm, and forrate control in converters and nonconverters was set up. Outcomemeasures were conversion within 12 h; time to conversion; earlyrate control; and stable slowing within 12 h. METHODS: We studied 40 patients with recent onset (<1 week) atrialfibrillation; controls received saline intravenously, the otherpatients digoxin 1·25 mg. RESULTS: One patient converted before digoxin administration. Conversionoccurred in 9/19 patients on digoxin and in 8/20 on placebo(ns). The mean time to conversion tended to be shorter onlyfor digoxin. Two late conversions on placebo were observed within24 h. Heart rate during atrial fibrillation decreased after30 min for converters and non-converters (P<0·05).For all patients on digoxin, heart rate after 30 min was lowercompared to baseline (P<0·002) and to placebo (P<0·02).Persistent, stable slowing occurred only in 3/10 non-converterson digoxin (P<0·05), and two patients developed bradyarrhythmias.QTc was shortened immediately after conversion in all patients.Converters had baseline characteristics similar to those ofnon-converters. CONCLUSIONS: Intravenous digoxin offers no substantial advantages over placeboin recent onset atrial fibrillation with respect to conversion,and provides weak rate control.     

Rhythm-independent feature of heart rate dynamics common to atrial fibrillation and sinus rhythm in patients with paroxysmal atrial fibrillation

OBJECTIVES: To examine if the long-range correlation in heart rate variability is a rhythm-independent characteristic common to both atrial fibrillation (AF) and sinus rhythm (SR) periods in patients with paroxysmal atrial fibrillation (PAF). METHODS: Holter electrocardiography was analyzed during sleep in 18 patients with paroxysmal atrial fibrillation during the atrial fibrillation (PAF-AF) and sinus rhythm (PAF-SR) periods, and also in 19 healthy controls with sinus rhythm (CTR-SR). The heart rate dynamics were assessed with the power-law spectral exponent (slope) of the log-log power spectrum between 0.0001 Hz and the breakpoint frequency. RESULTS: The slope showed a significant correlation between PAF-SR and PAF-AF (r = 0.614, p < 0.01). During sinus rhythm, the slope in paroxysmal atrial fibrillation with cardiovascular disease [PAF-SR (cvd+)] was steeper than that in paroxysmal atrial fibrillation without cardiovascular disease [PAF-SR (cvd-)] (p < 0.05). Although the slope was comparable between PAF-SR (cvd-) and CTR-SR, the slope in PAF-SR (cvd+) was steeper than that in CTR-SR (p < 0.05). A similar tendency was shown during atrial fibrillation. The slope in paroxysmal atrial fibrillation with cardiovascular disease [PAF-AF (cvd+)] was steeper than that in paroxysmal atrial fibrillation without cardiovascular disease [PAF-AF (cvd-)] (p < 0.05). Although the slope was comparable between PAF-AF (cvd-) and CTR-SR, the slope in PAF-AF (cvd+) tended to be steeper than that in CTR-SR. CONCLUSIONS: The long-range correlation in heart rate variability during sleep was a rhythm-independent characteristic and so may have a similar clinical value during atrial fibrillation and sinus rhythm in patients with paroxysmal atrial fibrillation.     

Safe and effective conversion of persistent atrial fibrillation to sinus rhythm by intravenous AZD7009

BACKGROUND: Acute drug conversion of persistent atrial fibrillation usually fails. OBJECTIVES: The purpose of this study was to test the proarrhythmic potential, safety, and efficacy of the novel antiarrhythmic agent AZD7009 in patients with persistent atrial fibrillation (AF) or atrial flutter (mean duration 43 days) scheduled for direct current (DC) cardioversion. METHODS: Patients were randomized to AZD7009 (3-hour intravenous infusion; n = 86) or placebo (n = 36). AZD7009 was given in doses intended to produce target pseudo-steady-state plasma levels of 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, or 2.5 micromol/L after 30 minutes of infusion. DC cardioversion was performed if conversion to sinus rhythm (SR) did not occur within 2 hours of infusion. RESULTS: AZD7009 in a concentration-dependent manner increased the rate of conversion of AF to SR and shortened the time to conversion. At the three highest target concentrations of AZD7009, 45%, 64%, and 70% of AF patients converted after a mean time of 62, 55, and 26 minutes, respectively, whereas no placebo-treated patients converted. SR was maintained for 24 hours in 21 of 22 patients with drug-associated conversion. AZD7009 treatment was associated with QT-interval prolongation; the increase in QT corrected according to Fridericia typically ranged from 40 to 80 ms at targeted pseudo-steady-state plasma concentrations >or=0.75 micromol/L, but a number of outliers with QT corrected according to Fridericia >550 ms were seen in the higher concentration groups, particularly after conversion to SR and prolonged infusion. None of the patients exhibited torsades de pointes according to predefined criteria; however, one patient exhibited a nonsustained, polymorphic ventricular tachycardia of eight beats with torsades de pointes-like features after AZD7009 infusion (asymptomatic and discovered only upon retrospective Holter tape analysis). Clinical adverse events (primarily dizziness, bradycardia, hypotension, and nausea) were significantly more common in the highest target concentration AZD7009 group vs placebo (P <.001). CONCLUSION: AZD7009 exhibited dose-dependent effects in converting AF to SR in AF patients and appeared to be associated with a low risk of proarrhythmia despite continued administration during a period of heightened vulnerability.     

Increased incidence of spontaneous conversion to sinus rhythm in patients with paroxysmal atrial fibrillation]

BACKGROUND. The aim of our study was to evaluate spontaneous conversion rate to sinus rhythm in patients with paroxysmal atrial fibrillation (AF) not submitted to any treatment (pharmacological and/or electrical). METHODS. From January 1985 to September 1990, 123 consecutive patients with paroxysmal AF were hospitalized in our department. In 11 patients arrhythmia was due to arrhythmogenic conditions; 34 patients were submitted to emergency treatment with drugs (23 cases) or electrical cardioversion (11 cases); 78 patients (41 males; mean age 65.1 years; 37 females: mean age 68.6 years), without emergency problems were enrolled in our study and were submitted to a four-day observation period without any therapy, except in case of worsening. 35 patients were free from heart disease; in the other 43, 28 had chronic coronary disease, 11 hypertensive cardiovascular disease, 2 rheumatic valvular disease, 1 hypertrophic cardiomyopathy and 1 chronic cor pulmonale. RESULTS. In all 78 patients sinus rhythm was restored spontaneously - in about 90% of them within 24 hours. Mean time to conversion was 21 hours (range 1-96 hours). Cardioversion occurred in similar percentage and at the same time in both subgroups of patients (with and without heart disease). CONCLUSIONS. Therefore, given the risks and cost of every treatment, a 24-hour observation period without therapy could be useful in those patients presenting with paroxysmal atrial fibrillation without emergency problems.     

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.     

Intravenous flecainide versus verapamil for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm

In a single-blind randomized study, the efficacy of intravenous flecainide (2 mg/kg/10 minutes) versus verapamil (10 mg/1 minute) was assessed in 40 patients with paroxysmal atrial fibrillation (AF) or atrial flutter (AFI). The treatment was considered successful if sinus rhythm occurred within 1 hour. Of 20 patients receiving flecainide, 14 of 17 (82%) with AF converted to sinus rhythm, but in 3 patients with AFI flecainide failed. All patients treated with verapamil (17 AF, 3 AFI) showed lower ventricular rates after 1 hour; however, only 1 (6%) with AF converted to sinus rhythm and 1 (6%) converted to AFI. Patients who did not convert to sinus rhythm after treatment with verapamil were treated with flecainide and observed for another hour. After the change to flecainide, 9 of 15 patients (60%) with AF still converted. Thus, 23 of 32 patients (72%) with AF and none of 7 with AFI converted to sinus rhythm after treatment with flecainide. Conversion to sinus rhythm was achieved in 19 of 22 patients (86%) when AF lasted less than 24 hours and in 4 of 10 (40%) when the arrhythmia lasted greater than 24 hours. Transient adverse effects were noted in 10 patients (26%) after flecainide. In summary, flecainide is an effective and safe drug for conversion of paroxysmal AF to sinus rhythm, but ineffective for AFI. Verapamil appears to be of no use for conversion of AF or AFI to sinus rhythm.     

Atrial contractile function and fibrosis in patients with paroxysmal atrial fibrillation in sinus rhythm

Objectives:The aim of the study was to investigate atrial contractile function in patients with paroxysmal atrial fibrillation (AF) in sinus rhythm using transthoracic echocardiography (EchoCG).Methods and results:Thirty-five patients with paroxysmal AF and arterial hypertension (mean age 62 ± 10 years, 43% male) in sinus rhythm were enrolled in the study. The control group was composed of comparable patients with arterial hypertension without heart rhythm disturbances. EchoCG was performed during sinus rhythm according to an extended protocol, which included the ejection fraction (EF) of the left atrium (LA) and tissue Doppler measurements. Myocardial fibrosis was assessed quantitatively by videodensitometry in intraventricular and intraatrial (IAS) septa using an original image post-processing algorithm. We found a significant decrease in the left atrial contraction function during sinus rhythm in patients with AF when compared to controls. LA EF (34 ± 14 vs. 54 ± 17, p = 0.03) and A’ velocity (0.17 ± 0.04 vs. 0.22 ± 0.04, p = 0.008) decreased while A/A’ ratio (2.7 ± 0.2 vs. 1.9 ± 0.1, p = 0.006) increased. Peak A velocity was not affected. Videodensitometric analysis revealed a 2.3-fold increase in IAS fibrosis fraction in AF patients compared with controls (p = 0.01).Conclusion:Patients with AF in sinus rhythm have markedly depressed atrial contractile function. Videodensitometry of IAS has the potential to be used as inexpensive method of atrial fibrosis assessment in patients with AF.     

High-density mapping of left atrial endocardial activation during sinus rhythm and coronary sinus pacing in patients with paroxysmal atrial fibrillation

INTRODUCTION: This study was designed to record global high-density maps of left atrial endocardial activation during sinus rhythm and coronary sinus pacing. METHOD AND RESULTS: Noncontact mapping of the left atrium was performed in nine patients with paroxysmal atrial fibrillation undergoing pulmonary vein ablation procedures. High-density isopotential and isochronal activation maps were superimposed on three-dimensional reconstructions of left atrial geometry. Mapping was repeated during pacing from sites within the coronary sinus. Earliest left atrial endocardial activation occurred anterior to the right pulmonary veins in seven patients and on the anterosuperior septum in two patients. A line of conduction block was seen in the posterior wall and inferior septum in all patients. The direction of activation in the left atrial myocardium overlying the coronary sinus was different from the electrogram sequence in the coronary sinus catheter in 6 of 9 patients. During coronary sinus pacing, activation entered the left atrium a mean (SD) of 41 (13) ms after the pacing stimulus at a site 12 (10) mm from the endocardium overlying the pacing electrode. Lines of conduction block were present in the posterior wall and inferior septum. CONCLUSION: In patients with paroxysmal atrial fibrillation, lines of conduction block are present in the left atrium during sinus rhythm and coronary sinus pacing. Electrograms recorded in the coronary sinus infrequently correspond to the direction of activation in the overlying left atrial myocardium.