Effects of dauricine, quinidine, and sotalol on action potential duration of papillary muscles in vitro.
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AIM: To compare the characteristics of dauricine, sotalol, and quinidine on action potential duration (APD). METHODS: Using intracellular microelectrode method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20 mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5 +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10 mumol.L-1 were less effective in lengthening APD at short cycle lengths. The effect of quinidine and sotalol on APD exhibited reverse use-dependence. CONCLUSSION: The effect of dauricine on APD depends on activation frequency. (+info)
Superiority of ibutilide (a new class III agent) over DL-sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group.
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OBJECTIVE: To compare the efficacy and safety of a single dose of ibutilide, a new class III antiarrhythmic drug, with that of DL-sotalol in terminating chronic atrial fibrillation or flutter in haemodynamically stable patients. DESIGN: Double blind, randomised study. SETTING: 43 European hospitals. PATIENTS: 308 patients (mean age 60 years, 70% men, 48% with heart disease) with sustained atrial fibrillation (n = 251) or atrial flutter (n = 57) (duration three hours to 45 days) were randomised to three groups to receive a 10 minute infusion of 1 mg ibutilide (n = 99), 2 mg ibutilide (n = 106), or 1.5 mg/kg DL-sotalol (n = 103). Infusion was discontinued at termination of the arrhythmia. MAIN OUTCOME MEASURE: Successful conversion of atrial fibrillation or flutter, defined as termination of arrhythmia within one hour of treatment. RESULTS: Both drugs were more effective against atrial flutter than against atrial fibrillation. Ibutilide was superior to DL-sotalol for treating atrial flutter (70% and 56% v 19%), while the high dose of ibutilide was more effective for treating atrial fibrillation than DL-sotalol (44% v 11%) and the lower dose of ibutilide (44% v 20%, p < 0.01). The mean (SD) time to arrhythmia termination was 13 (7) minutes with 2 mg ibutilide, 19 (15) minutes with 1 mg ibutilide, and 25 (17) minutes with DL-sotalol. In all patients, the duration of arrhythmia before treatment was a predictor of arrhythmia termination, although this was less obvious in the group that received 2 mg ibutilide. This dose converted almost 48% of atrial fibrillation that was present for more than 30 days. Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were not predictive of arrhythmia termination. Bradycardia (6.5%) and hypotension (3.7%) were more common side effects with DL-sotalol. Of 211 patients given ibutilide, two (0.9%) who received the higher dose developed polymorphic ventricular tachycardia, one of whom required direct current cardioversion. CONCLUSION: Ibutilide (given in 1 or 2 mg doses over 10 minutes) is highly effective for rapidly terminating persistent atrial fibrillation or atrial flutter. This new class III drug, under monitored conditions, is a potential alternative to currently available cardioversion options. (+info)
Comparison of sotalol with amiodarone for long-term treatment of spontaneous sustained ventricular tachyarrhythmia based on coronary artery disease.
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AIM: To compare the efficacy of sotalol versus amiodarone for long-term treatment of ventricular tachyarrhythmias. METHODS: Patients (n=75) with spontaneous, sustained ventricular tachyarrhythmias secondary to remote myocardial infarction were studied. After intravenous electrophysiological testing, both sotalol and amiodarone were predicted to be ineffective in 50 (67%) patients. Five patients were excluded. Forty-five patients were randomized to receive sotalol (n=22) or amiodarone (n=23) for maintenance therapy. The primary outcome variable was the time to first recurrence of sustained ventricular tachyarrhythmia. RESULTS: At 36 months. 75% of those allocated sotalol remained free of ventricular tachyarrhythmia compared with 38% of those allocated amiodarone (P=0.05). On multivariate analysis the risk of recurrence of ventricular tachyarrhythmia for patients on amiodarone was 5.9 times higher (P=0.008) than that for patients on sotalol. CONCLUSION: Sotalol is superior to amiodarone for long-term treatment of ventricular tachyarrhythmia secondary to coronary artery disease when both drugs have been predicted to be ineffective at intravenous electrophysiological testing. Randomized trials in larger numbers of patients with ventricular tachyarrhythmia need to be performed comparing the two agents directly. (+info)
QT dispersion in patients with arrhythmogenic right ventricular dysplasia.
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AIMS: Arrhythmogenic right ventricular dysplasia is a rarely diagnosed cardiomyopathy, but a frequent cause of ventricular arrhythmia and sudden cardiac death. QT interval dispersion, measured as an interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of electrical instability. The present study was conducted to assess the occurrence of QT dispersion and its modulation during treatment with sotalol. Methods Twenty-five patients with the diagnosis of arrhythmogenic right ventricular dysplasia were studied retrospectively. Fourteen patients were considered low risk for malignant ventricular arrhythmia and sudden cardiac death, and 11 high risk due to documented sustained ventricular arrhythmia, cardiac arrest, or sudden cardiac death. Twenty five healthy volunteers served as control subjects. RESULTS: Dispersion of repolarization was significantly higher in patients than in control subjects (QTd and JTd: P<0.05). Dispersion of repolarization was equal in patients both with and without malignant arrhythmias. There was no significant change in dispersion after treatment with sotalol. Adjacent QT dispersion between leads V3-V4, V4-V5 and V5-V6, respectively, was higher in patients than in control subjects (P<0. 05), while no differences were seen in leads V1-V2 and V2-V3. CONCLUSION: QT interval dispersion is increased in patients with arrhythmogenic right ventricular dysplasia. However, the degree of dispersion is not related to the severity of symptoms, nor is it influenced by treatment with sotalol. (+info)
Long-term reproducibility of electrophysiologically guided therapy with sotalol in patients with ventricular tachyarrhythmias.
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OBJECTIVES: Goal of this study was to assess the long-term reproducibility of electrophysiologic drug testing in patients with ventricular tachyarrhythmias (VT/VF). BACKGROUND: Programmed ventricular stimulation (PVS) is still widely used to guide antiarrhythmic therapy in patients with sustained ventricular tachycardia/fibrillation (VT/VF). Sotalol is considered as one of the most effective drugs for VT/VF. Because there is no proof of long-term reproducibility of a successful drug test with sotalol, we investigated the long-term reproducibility of drug testing with sotalol. METHODS: Thirty patients with VT/VF (age: 57+/-11 years, 20 patients with coronary heart disease, 7 patients with no structural heart disease, 3 with others) and reproducible induction of VT/VF (28 patients VT, two patients VF) in a baseline PVS, were suppressible with sotalol (mean dosage 395+/-137 mg) in a subsequent PVS. After a mean follow-up of 13+/-10 months a PVS was again performed in patients, who had no evidence of progressive cardiac disease, who did not experience any arrhythmia recurrences or who were drug compliant. Irrespective of the inducibility after long-term therapy with sotalol, all patients were kept on the initial sotalol regimen. All 30 patients had a stable cardiac condition, were free of VT/VF recurrences and were drug compliant. RESULTS: Despite the clinical efficacy of sotalol, in 12 patients (40%) VT/VF could again be induced after 13+/-10.2 months. Inducibility was independent of age, heart disease, ejection fraction and follow-up time. During a further follow-up of 22.1+/-10.9 months, five patients experienced nonfatal VT recurrences independently of the prior inducibility. CONCLUSIONS: This study shows a lacking long-term reproducibility of an initial effective PVS with sotalol. Despite an uneventful clinical follow-up, late electrophysiologic testing showed a VT/VF inducibility in a high portion of patients. Hence, electrophysiologic testing performed late after the initial drug test may no longer be predictive of outcome. (+info)
Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group.
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BACKGROUND: Patients with implantable cardioverter-defibrillators often receive adjunctive antiarrhythmic therapy to prevent frequent shocks. We tested the efficacy and safety of sotalol, a beta-blocker with class III antiarrhythmic effects, for this purpose. METHODS: In a multicenter trial, patients were stratified according to left ventricular ejection fraction (< or =0.30 or >0.30), randomly assigned to double-blind treatment with 160 to 320 mg of sotalol per day (151 patients) or matching placebo (151 patients), and followed for 12 months. Kaplan-Meier analyses of the time to an event were performed. Three end points were used: the delivery of a first shock for any reason or death from any cause, the first appropriate shock for a ventricular arrhythmia or death from any cause, and the first inappropriate shock for a supraventricular arrhythmia or death from any cause. RESULTS: Compliance with double-blind treatment was similar in the two groups. There were seven deaths in the placebo group and four in the sotalol group. As compared with placebo, treatment with sotalol was associated with a lower risk of death from any cause or the delivery of a first shock for any reason (reduction in risk, 48 percent; P<0.001 by the log-rank test), death from any cause or the delivery of a first appropriate shock (reduction in risk, 44 percent; P=0.007), or death from any cause or the delivery of a first inappropriate shock (reduction in risk, 64 percent; P=0.004). Sotalol also reduced the mean (+/-SD) frequency of shocks due to any cause (1.43+/-3.53 shocks per year, as compared with 3.89+/-10.65 in the placebo group; P=0.008). In the sotalol group, the reduction in the risk of death from any cause or the delivery of a first shock for any reason did not differ significantly between patients with ejection fractions of more than 0.30 and those with ejection fractions of 0.30 or less. CONCLUSIONS: Oral sotalol was safe and efficacious in reducing the risk of death or the delivery of a first defibrillator shock whether or not ventricular function was depressed. (+info)
An open label, randomised, crossover study comparing sotalol and atenolol in the treatment of symptomatic paroxysmal atrial fibrillation.
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OBJECTIVE: To compare sotalol and atenolol in the treatment of symptomatic paroxysmal atrial fibrillation. DESIGN: Prospective, randomised, open label, crossover study. SETTING: University hospital. PATIENTS: 47 subjects aged over 50 years were recruited from the hospital outpatient department following ECG documentation of paroxysmal atrial fibrillation that coincided with symptoms. Six patients withdrew and 41 completed the trial. INTERVENTIONS: Patients were randomised to one month's treatment with sotalol 80 mg twice daily or atenolol 50 mg once daily. Treatment arms were then crossed over. Patients underwent 72 hour Holter monitoring before randomisation and repeat studies were carried out at the end of both treatment periods. Symptom assessments were completed using linear analogue scales and the Nottingham health profile. MAIN OUTCOME MEASURE: Frequency of paroxysmal atrial fibrillation; secondary outcome measures included average and total duration of paroxysmal atrial fibrillation, total ectopic count, and symptom assessments. RESULTS: A reduction in the number and duration of episodes of paroxysmal atrial fibrillation was noted following treatment with sotalol and atenolol. There was no difference in frequency of paroxysmal atrial fibrillation during treatment with sotalol or atenolol (median difference 0; 95% confidence interval (CI) 0 to 1; p = 0.47). There was no difference in total duration of paroxysmal atrial fibrillation (median difference 0 min; 95% CI -1 to 2; p = 0. 51) or in average duration (median difference 0 min; 95% CI 0 to 1; p = 0.31). No difference was found in total ectopic count between sotalol and atenolol (median difference -123; 95% CI -362 to 135; p = 0.14). Treatments were equally tolerated with no difference in linear analogue scores for symptoms of paroxysmal atrial fibrillation (median difference -5; 95% CI -20 to 5; p = 0.26) or in all categories of the Nottingham health profile. CONCLUSIONS: No difference was found in terms of ECG or symptomatic control of paroxysmal atrial fibrillation between prescribing sotalol 80 mg twice daily and atenolol 50 mg once daily. There was an improvement in paroxysmal atrial fibrillation from baseline following treatment with either sotalol or atenolol. (+info)
Factors affecting epicardial dispersion of repolarization: a mapping study in the isolated porcine heart.
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OBJECTIVE: Non-uniform drug-induced prolongation of repolarization predominating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, the absence of M cells in immature animals, especially the pig, suggests other possible underlying mechanisms. We sought to examine, in this species, the effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. METHODS: Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-old pigs. Activation-recovery intervals were measured simultaneously from 128 unipolar electrograms. RESULTS: Baseline iso-interval maps were dipolar (41%) or multipolar (59%). Dispersion of repolarization was reverse frequency-dependent but was unaffected by lowering [K+]o. DL-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, whereas intramural recordings did not demonstrate any predominant effect in midmyocardial layers. Phenylephrine (1 mumol/l) notably augmented DL-sotalol effects. After [Mg++]o lowering, although dispersion was not significantly increased, DL-sotalol was associated with the spontaneous occurrence of polymorphic ventricular tachycardia in seven out of nine experiments. When maps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an arc of functional dissociation was observed in the vicinity of a steep gradient of repolarization in two out of nine tachycardias. CONCLUSION: Epicardial dispersion of repolarization is increased by slow rates, DL-sotalol and phenylephrine but is not the only requirement for initiation of polymorphic ventricular tachycardia. In combination with other factors, it helps continuation of the arrhythmia in this model. (+info)