心房颤动导管消融术后抗心律失常药物与复发的关系

目的探讨抗心律失常药物对心房颤动(简称房颤)导管消融术后早期复发和晚期复发的影响。方法210例房颤患者在三维电解剖标测系统和肺静脉环状标测电极联合指导下行环肺静脉电隔离。术后应用抗心律失常药物3个月,其中服用普罗帕酮29例、胺碘酮113例、索他洛尔3例,未服用药物65例,因索他洛尔组病例数少仅对前三组进行分析。早期复发定义为导管消融3个月内发生快速性房性心律失常,晚期复发定义为导管消融3个月后停用抗心律失常药物后发生快速性房性心律失常。结果三组平均年龄具有显著差异,余基线资料无显著性差异。术后3个月内共88例(41.9%)出现早期复发,普罗帕酮、胺碘酮、未服用抗心律失常药物三组早期复发率分别为41.4%,32.7%,55.4%,具有显著差异(P=0.013)。Logistic分析显示胺碘酮与早期复发独立相关(比数比=0.37,95%可信区间0.19～0.72,P=0.003)。随访180±75(91～374)天,66例(31.4%)晚期复发,三组晚期复发率分别为34.5%,28.3%,32.3%,无显著差异(P=0.752)。Logistic分析显示抗心律失常药物不是晚期复发的独立危险因素(P=0.978)。服索他洛尔3例均出现早期复发和晚期复发。结论术后服用抗心律失常药物特别是胺碘酮可显著降低房颤导管消融的早期复发,但对晚期复发无影响。     

右旋索他洛尔对室性心动过速伴射血分数降低患者的长期抗心律失常作用和安全性

对左室功能受损的患者发生严重室性心律失常时,理想的抗心律失常药选择十分困难。因为所有Ⅰ、Ⅱ、Ⅳ类抗心律失常药均降低心肌收缩力,Ⅲ类药中的胺碘酮虽在治疗剂量下无心脏抑制作用,但它有许多不良反应。而索他洛尔则在诸多抗心律失常药中具有相当特殊的地位。其(+)-对映体通常称为右旋索他洛尔(d-索他洛尔),是一种没有     

心脏外科手术后心律失常的药物治疗

心房颤动(简称房颤)和恶性室性心律失常是心脏手术后需要防治的心律失常。术前使用具有β受体阻滞活性的药物如β受体阻滞剂、胺碘酮和索他洛尔可预防房颤的发生。对于心功能不全或有器质性心脏病的术后房颤而不急需电复律者可选择胺碘酮转复和维持;对没有心力衰竭者,可选胺碘酮、索他洛尔或伊布利特,亦可选择IA类抗心律失常药转复。对房颤心室率控制的一线用药是β受体阻滞剂,也可选择胺碘酮或地尔硫卓。对于快速性室性心律失常一般选择静脉注射β受体阻滞剂美托洛尔;有心功能损害者,宜使用胺碘酮。对血流动力学不稳定的室性心律失常首选电复律;稳定者,药物复律首选胺碘酮,其次是利多卡因。     

索他洛尔临床应用进展

近年来心律失常抑制试验 (CAST)研究表明 , 类抗心律失常药 (氟卡胺、恩卡胺和莫雷西嗪 )虽然能抑制心肌梗死 (MI)后病人的室性心律失常 ,但却使治疗组死亡率较安慰剂组增高。CAST研究之后 ,临床医生将兴趣转向了 类药物的研究 ,主要集中选用了胺碘酮和索他洛尔与其它多种抗心律失常药物的对比研究。本文就索他洛尔 (施太可 )近年来在临床研究方面的进展作一概述。1　电生理和药理作用索他洛尔是左旋和右旋盐酸索他洛尔的外消旋混合物 ,左旋异构体具有 类 (β阻滞 )和 类抗心律失常双重作用 ,右旋异构体主要起 类抗心律失常作用 [1]…     

长期服用小剂量胺碘酮及索他洛尔致尖端扭转性室性心动过速一例

“长期服用小剂量胺碘酮及索他洛尔致尖端扭转性室性心动过速一例”是不合理使用抗心律失常药物导致严重后果的 1个典型病例。在心肌梗死后 ,包括伴有左心功能不全的患者 ,如有明确适应证 ,使用胺碘酮比较安全。在此例患者已用胺碘酮的基础上加用另一个明显延长复极的药物索他洛尔 ,即使剂量很小 ,仍导致反复的尖端扭转性室性心动过速发作。停用此二药后 ,无尖端扭转性室性心动过速复发。患者当时血钾 4.0 7mm ol/ L,可除外低钾血症的因素。因此 ,当联合使用抗心律失常药物时一般不应选用副作用 ,尤其致 (促 )心律失常作用相同、相加的药物     

胺碘酮和索他洛尔在心律失常治疗中的疗效及安全性比较

目的 比较临床常用的Ⅲ类抗心律失常药物胺碘酮和索他洛尔在心律失常治疗中的疗效及安全性,为临床用药提供依据.方法 选取我院2011年1月至2012年1月诊治的92例心律失常患者为研究对象,采用随机数字表法将其分为2个研究组,每组46例.两组分别使用口服胺碘酮与索他洛尔进行治疗.对所有研究对象进行心电图监测,并分别于治疗3个月、6个月、9个月、12个月、15个月及18个月对两组研究对象的转复率、转复时间及不良发应发生率进行比较及统计学分析.结果 胺碘酮组的转复率略高于索他洛尔组,但差异无统计学意义（P＞0.05）;胺碘酮组的转复时间长于索他洛尔组,且差异具有统计学意义（P＜0.05）;胺碘酮组的不良反应发生率为19.6％,低于索他洛尔组的28.3％,差异有统计学意义（P＜0.05）.结论 相对于索他洛尔,胺碘酮在心律失常的治疗中具有疗效显著、安全性更高等优势,且适用范围广泛,具有重要的临床价值,适于推广使用.     

心律失常的药物治疗——问题和挑战

本期4篇有关心律失常药物治疗的文章值得一读.当充分认识到现有Ⅰ类和Ⅲ类抗心律失常药物的局限性之后,在临床实践中我们常陷入困境. 自1914年发明奎尼丁以来,上世纪50 ～ 80年代,多种抗心律失常药物登台.包括利多卡因、普鲁卡因酰胺、双异丙吡胺、胺碘硐、美西律、氟卡胺、莫雷西嗪、普罗帕酮、索他洛尔等.为心律失常的药物治疗提供了多种选择.但是1989年著名的CAST试验揭示了这些抗心律药物的局限性,特别是在心力衰竭和缺血性心脏病患者,Ⅰ类抗心律失常药物使死亡率增加.长期使用胺碘酮,严重的器官不良     

胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用的实验研究

目的分析胺碘酮、索他洛尔与d-索他洛尔对犬心室肌细胞电生理作用.方法采用标准玻璃微电极技术,观察胺碘酮、d,l-索他洛尔(即索他洛尔)与d-索他洛尔对犬心室肌细胞动作电位时程(APD)及跨壁复极离散(TDR)的作用,以研究三种药物不同的促心律失常发生率的机制.结果胺碘酮(5μM)对心室壁三层细胞APD作用不一,使M细胞的APD90缩短,而内、外膜的APD90延长,TDR降低.索他洛尔(100μM)使心室壁三层细胞APD90均延长,对M细胞APD延长更明显,使TDR增加.d-索他洛尔(100μM)使心室壁三层细胞APD90均增加,但以M细胞APD90增加最为显著,而且随着d-索他洛尔诱发早期后除极、APD交替变异发生,而在心室肌内、外膜细胞则未见上述变化.结论胺碘酮、索他洛尔及d-索他洛尔三种药物的不同促心律失常作用与其对心室TDR的作用不同有关.     

胺碘酮与索他洛尔治疗心房颤动的Meta分析

目的 评价胺碘酮和索他洛尔治疗心房颤动（房颤）的有效性和安全性.方法 计算机检索Cochrane图书馆、PubMed、EMBASE、CBM、CNKI、VIP等数据库,并辅以Google Scholar等检索,收集有关胺碘酮和索他洛尔对比治疗房颤的随机对照试验（RCT）,由2名参与者独立评价纳入研究质量、提取资料,对两药房颤转复率、复发率及不良反应采用RevMan 5.0软件进行Meta分析.结果 共纳入14个RCT（1 508例患者）;Meta分析结果显示胺碘酮与索他洛尔房颤转复率及不良反应无统计学差异,胺碘酮防止房颤复发作用优于索他洛尔（比数比=0.49,95%可信区间为0.31～0.75,P=0.001）.结论 胺碘酮与索他洛尔在小剂量范围内均较为安全,前者降低房颤复发率效果较好.     

抗心律失常药物和植入式除颤器的比较:需作随机对照研究

本文评价植入式心脏除颤器(ICD)临床研究的现状和存在的问题。并介绍评价抗心律失常药物(索他洛尔、胺碘酮)和ICD治疗的随机对照研究计划。     

A Review of Clinical Trials Assessing the Efficacy and Safety of Newer Antiarrhythmic Drugs in Atrial Fibrillation

Clinical trials assessing the efficacy of anti- arrhythmic drugs for terminating atrial fibrillation have demonstrated that rate control drugs have little to no added efficacy compared to placebo; however, spontaneous conversion of recent-onset atrial fibrillation is common. Antiarrhythmic drugs such as oral dofetilide, oral bolus-flecainide and propafenone and intravenous ibutilide all have a role in terminating atrial fibrillation. Active comparator trials have demonstrated that amiodarone is more efficacious in maintaining sinus rhythm than propafenone and sotalol. Multiple trials have demonstrated the safety of amiodarone, sotalol, dofetilide and azimilide in a post-myocardial infarction population and amiodarone and dofetilide in a congestive heart failure population. Newer antiarrhythmic agents, some with novel mechanisms of action, will add to the pharmacologic armamentarium in treating atrial fibrillation.     

Canadian Cardiovascular Society atrial fibrillation guidelines 2010: rate and rhythm management

The goals of atrial fibrillation (AF) and atrial flutter (AFL) arrhythmia management are to alleviate patient symptoms, improve patient quality of life, and minimize the morbidity associated with AF and AFL. Arrhythmia management usually commences with drugs to slow the ventricular rate. The addition of class I or class III antiarrhythmic drugs for restoration or maintenance of sinus rhythm is largely determined by patient symptoms and preferences. For rate control, treatment of persistent or permanent AF and AFL should aim for a resting heart rate of <100 beats per minute. Beta-blockers or nondihydropyridine calcium channel blockers are the initial therapy for rate control of AF and AFL in most patients without a history of myocardial infarction or left ventricular dysfunction. Digoxin is not recommended as monotherapy for rate control in active patients. Digoxin and dronedarone may be used in combination with other agents to optimize rate control. The first-choice antiarrhythmic drug for maintenance of sinus rhythm in patients with non structural heart disease can be any one of dronedarone, flecainide, propafenone, or sotalol. In patients with abnormal ventricular function but left ventricular ejection fraction >35%, dronedarone, sotalol, or amiodarone is recommended. In patients with left ventricular ejection fraction <35%, amiodarone is the only drug usually recommended. Intermittent antiarrhythmic drug therapy ("pill in the pocket") may be considered in symptomatic patients with infrequent, longer-lasting episodes of AF or AFL as an alternative to daily antiarrhythmic therapy. Referral for ablation of AF may be considered for patients who remain symptomatic after adequate trials of antiarrhythmic drug therapy and in whom a rhythm control strategy remains desired.     

Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs

One hundred nine patients with recurrent episodes of symptomatic atrial fibrillation or flutter, or both, who had failed one to five previous antiarrhythmic drug trials were treated with propafenone and, subsequently, sotalol if atrial fibrillation recurred. The clinical profile of the study group was as follows: age 63 +/- 13 years, left atrial anteroposterior dimension 4.4 +/- 0.9 cm and left ventricular ejection fraction 57 +/- 14%. Paroxysmal atrial fibrillation occurred in 56 patients (51%) and chronic atrial fibrillation occurred in 53 patients (49%). After loading and dose titration phases were completed, the maintenance doses of drugs were 450 to 900 mg/day for propafenone and 160 to 960 mg/day for sotalol. Life table estimates of the duration of freedom from atrial fibrillation were constructed for each drug trial. The percent of patients free of recurrent symptomatic arrhythmia at 6 months was 39% for propafenone and 50% for sotalol. The cumulative proportion of patients successfully treated with propafenone or sotalol, or both, by 6 months was 55% and remained relatively constant beyond that point. The incidence of intolerable side effects necessitating discontinuation of therapy ranged from 7% to 8%. Thus, despite previous unsuccessful drug trials, a substantial proportion of patients with recurrent symptomatic atrial fibrillation refractory to conventional therapy can be treated successfully and safely with newer antiarrhythmic drugs. Treatment failures tend to occur early in the course of follow-up, permitting easy identification of candidates for alternative therapeutic approaches.     

Anti-arrhythmic effect of oral propafenone. Apropos of 70 cases

During a 3 year period, seventy patients aged 53 +/- 16 years with a total of 73 arrhythmias were treated over a mean period of 6.8 months (maximum 27 months) with oral propafenone, the usual dose being 900 mg/day. The study covered the whole spectrum of cardiac arrhythmias (32 supraventricular, 41 ventricular), and their relation to the autonomic nervous system. The efficacy was scored from 1 (no effect) to 5 (complete control) as judged by the clinical response, the results of Holter monitoring (175 control and 133 test recordings on therapy), and a comparison was made between the effects of propafenone and other antiarrhythmics: quinidine-like drugs, beta-blockers and amiodarone. With respect to supraventricular arrhythmias: 9 cases of vagally-induced atrial flutter and fibrillation were unaffected by propafenone (mean score = 1.1). On the other hand, the drug was very effective (mean score = 4.1) in 8 cases of adrenergic atrial arrhythmias. In 12 arrhythmias with more varied mechanisms (extrasystoles, tachysystole, paroxysmal atrial fibrillation) an intermediate score was obtained (2.8). Three cases of resistant junctional tachycardia due to reentry were improved. At ventricular level, 5 cases of extrasystole sensitive to quinidine were also improved by propafenone (4.6); the difference was more clearcut in 8 cases of benign idiopathic tachycardia (propafenone: 4.1, and quinidine: 2.4). This was more marked in 13 cases of more severe arrhythmia in diseased hearts in which the effect of propafenone (4.1) was superior even to that of amiodarone. However, propafenone was less effective (3.3) than amiodarone in 4 cases of severe polymorphic idiopathic ventricular tachycardia closely related to the autonomic nervous system. The antiarrhythmic effect of propafenone was appreciable in 10 cases of resistant post-infarction ventricular tachycardia, eventually in association with amiodarone. Slowing of the sinus rhythm (-11.6%) with no change in the day/night ratio was due to beta-inhibition. However, in toxic doses this may progress to sinoatrial block (9 cases). A lengthening of the PR interval and duration of QRS was common, but this was not complicated by torsade de pointes, one case of which was successfully treated by propafenone. Secondary gastro-intestinal effects and vertigo were rarely severe enough to warrant stopping therapy. In conclusion, these results show that the introduction of propafenone is a valuable therapeutic advance in the treatment of arrhythmias, especially in those with a favoring adrenergic mechanism.     

Antiarrhythmic drugs

Opinion statement Both supraventricular and ventricular arrhythmias are associated with increased mortality and morbidity. Numerous antiarrhythmics have been developed in an attempt to decrease the frequency of these arrhythmias, hoping to improve survival and improve quality of life. Antiarrhythmic agents are a diverse group of drugs that affect various cardiac ionic channels and block specific arrhythmias. However, despite the suppression of these potentially lethal cardiac arrhythmias, only the β blockers have been shown to reduce sudden arrhythmic death, especially in patients with prior myocardial infarction or heart failure. Some antiarrhythmic agents can also worsen the index arrhythmia and caution must be used especially in the compromised patient. A simple guideline is as follows: For conversion of atrial fibrillation or flutter to sinus rhythm, in the absence of structural heart disease, intravenous ibutilide or oral propafenone or flecainide are good choices. For maintenance of sinus rhythm, propafenone or flecainide are logical choices. In the presence of structural heart disease, amiodarone, dofetilide, or dl sotalol are preferred. In heart failure, dofetilide or amiodarone are the logical choices. The role of antiarrhythmic therapy for ventricular arrhythmias is questionable and may be contraindicated, except for the use of β blockers. The implantable cardioverter-defibrillator is often used in patients at high risk. At times, the addition of an antiarrhythmic agent such as amiodarone may be justified.     

European experience with the antiarrhythmic efficacy of propafenone for supraventricular and ventricular arrhythmias

Seventy-one patients (mean age 53 years) were treated with oral propafenone, 900 mg/day, for a mean of 6.6 months. A large spectrum of arrhythmias was encountered, and particular attention was paid to their relation with the autonomic nervous system. Drug efficacy was graded from 1 (no effect) to 5 (complete control) according to the clinical result and Holter recording. This method permitted comparisons to be made between propafenone and 3 other antiarrhythmic agents: quinidine, beta-blockers and amiodarone. Among the 32 patients with supraventricular arrhythmias, 9 cases of vagally dependent atrial flutter and fibrillation were less sensitive to propafenone (mean effect 1.4) than to quinidine (mean effect 2.0) or amiodarone (mean effect 2.3). However, 8 cases of adrenergically dependent atrial tachycardia and fibrillation were more sensitive to propafenone (mean effect 4.1) than to beta blockers (3.0) or amiodarone (mean effect 3.5). In 12 cases of miscellaneous atrial arrhythmias the response to propafenone was intermediate. However, 3 patients with resistant junctional tachycardia were improved with propafenone. Among 42 ventricular arrhythmias, 5 patients with extrasystole who were responsive to quinidine (mean effect 3.8) were also improved with propafenone (mean effect 4.6). Propafenone (mean effect 4.1) was much more effective than quinidine (mean effect 2.4) in treating 8 cases of idiopathic benign ventricular tachycardia and even more successful in treating 13 cases of more severe arrhythmias in diseased hearts (propafenone's mean effect 4.1, quinidine's mean effect 1.9 and amiodarone's mean effect 1.9). Propafenone was less effective (mean effect 3.3) than amiodarone (mean effect 4.0) in 4 cases of severe, adrenergically dependent idiopathic ventricular tachycardia (VT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Amiodarone reduces procedures and costs related to atrial fibrillation in a controlled clinical trial.

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia, and engenders significant health care costs. The impact of various treatment options for atrial fibrillation on hospital costs has not been evaluated in a randomized trial. METHODS: We analysed 1-year follow-up data on 392 patients randomized to low dose amiodarone (200 mg. day(-1)) or alternative first-line therapy (sotalol or propafenone) in a multicentre trial (Canadian Trial of Atrial Fibrillation, CTAF). RESULTS: Patients in the amiodarone group had fewer electrical cardioversions (65 vs 109 for patients in the sotalol/propafenone group, P<0.0001), and pacemaker insertions (4 vs 11, P=0.07). The average amiodarone patient spent fewer days in hospital (0.47 vs 0.97, P=0.01), and incurred lower costs ($532 vs $898, P=0.03), for admissions where atrial fibrillation was the admitting diagnosis. Average total hospital costs per patient for all admissions, as well as average combined hospital and physician costs per patient, showed wide variations within the treatment arms and were not significantly different between groups. CONCLUSION: For patients in whom antiarrhythmic drug therapy is indicated, low dose amiodarone significantly reduces atrial fibrillation-related costs by reducing the number of atrial fibrillation-related procedures.     

Role of Amiodarone in the Era of the Implantable Cardioverter Defibrillator

Amiodarone is one of the most frequently used antiarrhythmic drugs in clinical practice. In patients with atrial fibrillation, in whom rhythm control is judged desirable, amiodarone is the most effective therapy. Amiodarone effectively prevents atrial fibrillation and may improve quality of life, but there is no evidence that it decreases mortality or severe morbidity in atrial fibrillation. In patients at risk for life-threatening ventricular arrhythmias, amiodarone may decrease mortality to a small degree, but the evidence for this benefit is incomplete. Patients with implantable cardioverter defibrillators frequently require antiarrhythmic drug therapy, especially to treat electrical storm. Amiodarone is useful in these patients; however, it may increase defibrillation thresholds in some patients. In patients with out-of-hospital DC shock-resistant VF, amiodarone is the most effective antiarrhythmic drug available to assist in resuscitation. Amiodarone is a complicated drug, and its optimal use requires careful patient surveillance with respect to potential adverse effects. (J Cardiovasc Electrophysiol, Vol. 14, pp. S78-S81, September 2003, Suppl.)     

Serial antiarrhythmic therapy: role of amiodarone in prevention of atrial fibrillation recurrence--a lesson from the HOT CAFE Polish Study

Antiarrhythmic drug prophylaxis is known to improve long-term success of electrical cardioversion (CV) in persistent atrial fibrillation (AF). This prospective study evaluates the efficacy of sequential antiarrhythmic drug therapy in sinus rhythm (SR) maintenance after successful elective CV in patients with persistent nonvalvular AF. MATERIALS AND METHODS: One hundred and twenty-eight patients (61+/-8 years old) with persistent AF underwent CV. Mean AF duration preceding CV was 268+/-99 days. Following SR restoration, patients were treated sequentially with either of the following antiarrhythmic drugs: propafenone, sotalol or disopyramide. Where arrhythmia recurred, patients received another CV and a new drug from the range defined above. Where such treatment failed, patients were loaded with 14.0- to 16.0-gram doses of amiodarone and a third CV was performed. If the first CV failed to restore SR, patients received a loading dose of amiodarone followed by another CV. When successful, amiodarone was administered on continuous basis. RESULTS: The first CV proved successful in 55.5% of patients. During 1-year of follow-up, 31 patients (43.7%) presented with SR were treated with one antiarrhythmic agent (median does not exist). Application of the second drug proved to be effective in 6 patients (15.0%; median 13 days). Amiodarone was administered as the third antiarrhythmic agent to patients who had AF recurrence on the first two antiarrhythmic agents (propafenone, sotalol or disopyramide). It proved to be effective in 18 patients (52.9%; median does not exist) remaining free from AF for a period of 1 year as of commencement of the sequential antiarrhythmic therapy. Fifty-seven patients, in whom the first CV was ineffective, received amiodarone. During the loading period, SR was restored in 7 patients (12.3%). The remaining 50 patients underwent repeated CV, with SR restored in 37 (74.0%) of them. Long-term amiodarone treatment maintained SR in 30 (68.2%) patients during the follow-up period. Amiodarone helped to maintain SR in a total of 56.5% of patients. CONCLUSIONS: Amiodarone seems to be the drug most effectively restoring and maintaining SR in patients with persistent AF resistant to CV and standard antiarrhythmic drug prophylaxis.     

Pharmacologic treatment of supraventricular tachycardia: the German experience.

Tachyarrhythmias that originate above the bifurcation of the bundle of His or in tissue proximal to it are classified as supraventricular tachyarrhythmias (SVTs). Primary treatment of SVT tries to influence the underlying disease. Symptomatic therapy is subdivided into drug therapy, electrotherapeutic tools (e.g., antitachycardia pacemakers, catheter ablation), and antiarrhythmic surgery. Antiarrhythmic agents that slow conduction and suppress premature beats are efficient for emergency and long-term treatment of SVTs. We evaluated some of the most relevant antiarrhythmic drugs in SVT, including propafenone, diprafenone, cibenzoline, sotalol, and diltiazem; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine, and flecainide are summarized. In 1990, the case load of supraventricular arrhythmias per physician in Germany was more than 30 patients seen per month. About 50% of them were treated with drug therapy; i.e., approximately 17 patients were treated with antiarrhythmic drugs per month per physician for supraventricular arrhythmias. The most important antiarrhythmic agents used in Germany are propafenone (40%), combination of quinidine and verapamil (23%), sotalol (12%), disopyramide (6%), flecainide (6%), and other (13%).