Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation

The efficacy and safety of amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation was examined by reviewing the trials on the subject identified through a comprehensive literature search. Amiodarone has been used both intravenously (i.v.) and orally for the pharmacological cardioversion of recent-onset atrial fibrillation. Intravenous amiodarone has been used as a bolus only or as a bolus followed by a continuous i.v. infusion until conversion or up to 24 h. The dose of i.v. bolus given ranged from 3 to 7 mg/kg body weight and that of infusion from 900 to 3000 mg/day. The efficacy reported is 34-69% with the bolus only regimens, and 55-95% with the bolus followed by infusion regimens. Only the higher dose (>1500 mg/day) amiodarone is superior to placebo in converting recent-onset atrial fibrillation to sinus rhythm. The highest 24-h conversion rates have been reported with the i.v. regimen of 125 mg/h until conversion or a maximum of 3 g and the oral regimen of 25-30 mg/kg body weight administered as a single loading-dose (>90% and >85%, respectively). Most of the conversions occur after 6-8 h of the initiation of therapy. Predictors of successful conversion are shorter duration of atrial fibrillation, smaller left atrial size, and higher amiodarone dose. Amiodarone is not superior to the other antiarrhythmic drugs conventionally used for the pharmacological cardioversion of recent-onset atrial fibrillation but is relatively safe in patients with structural heart disease and in those with depressed left ventricle function. Therefore, amiodarone could be used particularly in patients with structural heart disease and in those with left ventricular systolic dysfunction as the use of class IC drugs, propafenone and flecainide, for cardioversion of atrial fibrillation is contraindicated in such patients.     

Intravenous amiodarone for cardioversion of recent-onset atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is one of the most common causes of hospital admission, with a prevalence of up to 5% of the population, increasing with advancing age. Emergency direct current cardioversion is the therapy of choice when arrhythmia leads to hemodynamic compromise, but in patients who are hemodynamically stable, antiarrhythmic drugs are usually given to restore sinus rhythm. HYPOTHESIS: The study was undertaken to assess the efficacy of intravenous amiodarone in cardioversion of recent-onset paroxysmal atrial fibrillation (AF). No standard antiarrhythmic therapy has been accepted for pharmacologic cardioversion of AF. Amiodarone seems to be a promising candidate, but only few randomized trials are available and the results are inconsistent. METHODS: In all, 160 patients with AF lasting < 24 h were randomly assigned (2:1 fashion) to the amiodarone group (n = 106) receiving 5 mg/kg as a 30 min intravenous (i.v.) infusion, followed by i.v. infusion of 10 mg/kg during 20 h diluted in 1000 ml of 10% glucose with 20 IU of rapid-action insulin, 80 mEq of potassium chloride, and 8 g of magnesium sulphate (GIKM), or to the control group (n = 54) receiving 1000 ml of GIKM alone. Treatment was continued up to 20 h independent of sinus rhythm restoration. RESULTS: Sinus rhythm was restored 20 h after initiation of therapy in 88 (83%) patients in the amiodarone group and in 24 (44%) patients in the control group (p < 0.0001). The difference between efficacy of the two treatment modalities became significant already after 8 h of therapy (53 vs. 14 patients with sinus rhythm, respectively, p < 0.05). The mean dose of amiodarone administered until sinus rhythm restoration was 740 +/- 296 mg. The presence and the type of underlying heart disease did not influence the conversion rate in either group. In two patients (1.8%) treated with amiodarone, the return of sinus rhythm was preceded by asystole. CONCLUSION: Amiodarone is effective in the termination of AF lasting < 24 h. It may be particularly useful in patients with organic heart disease in whom class I antiarrhythmic agents may be contraindicated. During treatment, the heart rhythm should be monitored continuously.     

依布利特与普罗帕酮转复心房颤动的临床研究

目的　研究和比较新型Ⅲ类抗心律失常药物依布利特与普罗帕酮转复心房颤动 (房颤 )的有效性及安全性。方法　采用随机、单盲对照研究。共入选房颤持续 1 5h~89d的患者 69例,其中男性 28例,女性 41例,随机进入依布利特组(n=34)、普罗帕酮组(n=35)。前者于 10min内静脉注射依布利特 1mg,后者于 10min内静脉注射普罗帕酮 70mg,如给药结束 10min后仍未转复为窦性心律,各组重复前述治疗 1次。观察开始给药后 1 5h内房颤的转复率及 4h内的不良反应。结果　(1)依布利特转复房颤的成功率明显高于普罗帕酮(70 .59% vs42 .86%,P<0. 05); (2)房颤的转复率与房颤的持续时间有关,持续时间低于 24h的房颤转复率 ( 71 05%, 27 /38 )明显高于持续时间超过 24h者(38 71%, 12 /31,P<0. 01),其中依布利特对持续 24h之内的房颤转复率高达 83 .33% (15 /18); (3)房颤的转复率与左心房直径呈负相关,左心房直径 <4 0cm患者的转复率 ( 75 68%, 28 /37 )明显高于左心房直径≥4 0cm患者的转复率(34. 38%, 11 /32,P<0 01); (4)依布利特最严重的不良反应为非持续性单形室性心动过速,发生率为 8 .82% (3 /34);普罗帕酮最严重的不良反应为低血压 (2. 86%, 1 /35)及长间歇(RR间期>2 .0s, 11 .43%, 4 /35)。结论　依布利特是一种快速转复     

Efficacy and safety of vernakalant for cardioversion of recent-onset atrial fibrillation: A protocol for systematic review and meta-analysis

Background:Atrial fibrillation (AF) is the most common tachyarrhythmia encountered in clinical practice and is associated with substantial morbidity and mortality. This study aimed to determine the efficacy and safety of vernakalant for cardioversion of recent-onset AF.Methods:A comprehensive systematic literature search will be conducted in Cochrane Library, PubMed, Web of Science, EMBASE, for randomized controlled trials (RCTs) about the vernakalant with AF. Two reviewers will independently assess the quality of the selected studies according to the Cochrane Collaboration''s tool for RCTs. The bias risk of the RCT will be assessed by the Cochrane risk of bias (ROB) tool. The quality of the evidence will be evaluated by Grading of Recommendations Assessment Development and Evaluation (GRADE) system. Results from these questions will be graphed and assessed using Review Manager 5.3.Results:The results of this meta-analysis will be published in a peer-reviewed journal.Conclusion:This review will evaluate the safety and efficacy of vernakalant for patients with AF, provide more recommendations for patients or researchers, and high-level evidence for clinical decision-making.     

Amiodarone and its infusion velocity in recent-onset atrial fibrillation]

Two intravenous amiodarone dosing schedules in 28 patients with atrial fibrillation arisen less than 10 days before, were evaluated. Their effectiveness in converting to sinus rhythm, the incidence of side effects and the relationship between efficacy and plasma concentrations of amiodarone and desethylamiodarone were compared. Schedule A, with amiodarone infusion at a rate of 1.5 mg/kg/h up to two hours after the restoration of sinus rhythm or to a maximum dose of 1200 mg, reverted 86.7% of all patients. Schedule B, with a single amiodarone infusion of 300 mg over 15 minutes, followed by a 300 mg dose maintenance over three hours, reverted 69.2% of all patients. Schedule A was more effective than schedule B (P less than 0.01). Schedule B reverted before A (P less than 0.05). The only transient adverse effects were: superficial phlebitis, symptomatic hypotension and silent QTc lengthening. Amiodarone and desethylamiodarone plasma concentrations were not related to efficacy of the drug in converting sinus rhythm. In conclusion, an intravenous infusion of amiodarone over few hours showed high efficacy (79.6%), wide therapeutic index, good compliance and irrelevant adverse effects in converting patients with recent-onset fibrillation.     

Amiodarone after unsuccessful direct-current cardioversion of persistent atrial fibrillation

AIM: To assess the safety and efficacy of amiodarone used after unsuccessful direct current (DC) cardioversion of persistent atrial fibrillation (AF). METHODS: The study group comprised 67 patients (F/M 26/41; mean age 61.3+/-11.2 years) after unsuccessful DC cardioversion (DCC) of persistent AF (mean arrhythmia duration 212.6+/-135.2 days) in whom another attempt of DCC was intended. Repeat DC cardioversion was performed after loading with oral amiodarone, for a period necessary to achieve a cumulative dose of up to 12.0-16.0 g. Pretreatment was an outpatient procedure. After successful DC cardioversion all study subjects received a maintenance dose of amiodarone, 100-200 mg daily, aimed at preventing AF. The follow-up period was 12 months. RESULTS: Spontaneous conversion to sinus rhythm (SR) during amiodarone pretreatment was observed in 13 pts (19.2%). DCC was performed in 54 pts and SR was restored in 41 of the study pts (76%). Complications occurred in 3 pts, including 1 case of apparent hyperthyroidism and 2 cases of decreased TSH level, and required amiodarone withdrawal. After 12 months, 72.2% of pts maintained SR on low dose (179.2+/-42.1 mg/day) amiodarone. Spontaneous conversion to SR during amiodarone loading was significantly related to long-term SR maintenance after successful DC cardioversion (p<0.013; RR 2.01; 95% CI 1.34-3.03). CONCLUSION: Pretreatment with amiodarone and repeat DC cardioversion results in sinus rhythm restoration in about 80.6% of pts with persistent AF after an initial unsuccessful attempt. Direct-current cardioversion can be performed safely taking standard precautions for patients receiving amiodarone. At 12 months after successful repeated DC cardioversion, more than 72.2% of pts on low-dose amiodarone maintain SR.     

Oral loading single dose flecainide for pharmacological cardioversion of recent-onset atrial fibrillation

The efficacy and safety of the single oral loading dose of flecainide for cardioversion of recent-onset atrial fibrillation was examined by reviewing the trials on the subject identified through a comprehensive literature search. Most of the trials used a single dose of 300 mg for oral loading. The success rate ranged from 57 to 68% at 2-4 h and 75 to 91% at 8 h after drug administration. The conversion time ranged from 110+/-82 to 190+/-147 min, depending on the duration of observation after drug administration, which in most trials was of 8 h. Single oral loading regimen of flecainide was significantly more efficacious than placebo, and was as efficacious as the single oral loading regimen of propafenone. Both the single oral loading and the intravenous loading regimens of flecainide were equally efficacious but the intravenous regimen resulted in an earlier conversion. Adverse effects reported were mild non-cardiac side effects, reversible QRS complex widening, transient arrhythmias and left ventricular decompensation. The transient arrhythmias were chiefly at the time of conversion and included appearance of atrial flutter and sinus pauses. No life-threatening ventricular arrhythmia or death was reported. The single dose oral loading regimen of flecainide appears to be effective for cardioversion of recent-onset atrial fibrillation with a relatively rapid effect within 2-4 h, and is free of serious complications in patients without structural heart disease. Patients with substantial structural heart disease were excluded from most of the trials.     

Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation

The efficacy and safety of the single dose oral loading regimen of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation (AFib) was evaluated by analyzing the trials on the subject identified through a comprehensive literature search. Most of the trials used a single dose of 600 mg for oral loading. The success rates ranged from 56% to 83%, depending on the duration of AFib and follow-up after drug administration. The conversion time ranged from 110 +/- 59 to 287 +/- 352 min, depending on the duration of observation after drug administration. The single dose oral loading regimen of propafenone was significantly more efficacious than placebo in the first 8 h after administration but not at 24 h. Compared with the intravenous regimen, the oral regimen resulted in fewer conversions in the first 2 h, but both regimens were equally efficacious afterward. The oral propafenone regimen was as efficacious as the single dose oral loading regimen of flecainide but was superior to those of quinidine and amiodarone. The adverse effects reported were transient arrhythmia, reversible QRS-complex widening, transient hypotension and mild noncardiac side effects. The transient arrhythmias were chiefly at the time of conversion and included appearance of atrial flutter, bradycardia, pauses and junctional rhythm. No life-threatening proarrhythmic adverse effects were reported. The single oral loading dose of propafenone appears to be highly effective for conversion of recent-onset AFib, with a relatively rapid effect within 2 to 3 h and freedom from serious adverse effects.     

胺碘酮联合氯沙坦预防心房颤动复律后复发

目的观察胺碘酮联合氯沙坦治疗阵发性和持续性心房颤动复律后维持窦性心律的疗效。方法80例具有转复窦性心律指征的阵发性和持续性心房颤动患者随机分为两组,单用胺碘酮治疗组（n=40）和胺碘酮＋氯沙坦治疗组（n=40）,12个月后停用胺碘酮,共随访18个月,观察药物对两组患者窦性心律的维持率及心房重构的影响。结果随访第12月和18月,窦性心律维持率在单用胺碘酮治疗组分别为45．9％和35．1％,在胺碘酮＋氯沙坦治疗组分别为79．5％和56．0％;胺碘酮＋氯沙坦组显著高于胺碘酮组（P均〈0．05）。胺碘酮＋氯沙坦组转变为永久性心房颤动患者（8例）显著低于单用胺碘酮治疗组（13例）,（P〈0．05）。左心房直径在单用胺碘酮组治疗前后有显著变化[治疗前（37．7±6．2）mm,治疗18月后时39．2±6．5mm）（P〈0．05）],而胺碘酮＋氯沙坦组无显著改变[治疗前（38．1±5．8）mm,治疗18月后（38．4±6．1）mm]。结论胺碘酮联合氯沙坦能提高心房颤动复律后维持窦性心律的疗效和防止心房结构重构。     

Biphasic versus monophasic cardioversion in shock-resistant atrial fibrillation:

Biphasic versus Monophasic Cardioversion. INTRODUCTION: Cardioversion of atrial fibrillation using monophasic transthoracic shocks occasionally is ineffective. Biphasic cardioversion requires less energy than monophasic cardioversion, but its efficacy in shock-resistant atrial fibrillation is unknown. Thus, we compared the efficacy of cardioversion using biphasic versus monophasic waveform shocks in patients with atrial fibrillation previously refractory to monophasic cardioversion. METHODS AND RESULTS: Fifty-six patients with prior failed monophasic cardioversion were randomized to either a 360-J monophasic damped sinusoidal shock or biphasic truncated exponential shocks at 150 J, followed by 200 J and then 360 J, if necessary. If either waveform failed, patients were crossed over to the other waveform. The primary endpoint was defined as the proportion of patients achieving sinus rhythm following initial randomized therapy. Stepwise multivariate logistic regression examined independent predictors of shock success, including patient age, sex, left atrial diameter, body mass index, drug therapy, and waveform. Twenty-eight patients were randomized to the biphasic shocks and 28 to the monophasic shocks. Sinus rhythm was restored in 61% of patients with biphasic versus 18% with monophasic shocks (P = 0.001). Seventy-eight percent success was achieved in patients who crossed over to the biphasic shock after failing monophasic cardioversion, whereas only 33% were successfully cardioverted with a monophasic shock after crossover from biphasic shock (P = 0.02). Overall, 69% of patients who received a biphasic shock at any point in the protocol were cardioverted successfully, compared to 21% with the monophasic shock (P < 0.0001). The type of shock was the strongest predictor of shock success (P = 0.0001) in multivariate logistic regression. CONCLUSION: An ascending sequence of 150-, 200-, and 360-J transthoracic biphasic cardioversion shocks are successful more often than a single 360-J monophasic shock. Thus, biphasic shocks should be the recommended configuration of choice for all cardioversions.     

Amiodarone for refractory atrial fibrillation

Atrial fibrillation (AF) is a difficult arrhythmia to manage with antiarrhythmic agents. Amiodarone is highly effective in restoring and maintaining normal sinus rhythm in patients with AF. However, the mechanism and predictors of efficacy for amiodarone in treating AF have not been adequately addressed. Various measures of success or failure of amiodarone therapy were examined in 68 patients who had paroxysmal or chronic, established AF refractory to conventional antiarrhythmic agents. The patients were 25 to 75 years old (mean 59) and mean follow-up was 21 months (range 3 to 56). Maintenance amiodarone dosages were 200 to 400 mg/day. Overall, amiodarone therapy was effective long term in 54 of the 68 patients (79%). Left atrial diameter, age, gender and origin of AF were not helpful in predicting success or failure of amiodarone therapy. The presence of chronic AF for longer than 1 year was an adverse factor in maintaining normal sinus rhythm (p = 0.007), although the success rate even in this group was relatively high (57%). Thirty-five percent of the patients had adverse effects, which precluded long-term therapy with amiodarone in 10%.