Effects of amiodarone and diltiazem on persistent atrial fibrillation conversion and recurrence rates: a randomized controlled study

Purpose: To assess the effects of amiodarone and diltiazem on atrial fibrillation (AF) induced atrial electrical remodeling and their clinical implications. Methods: Persistent AF patients were randomly assigned to three treatment groups over a period from 6 weeks before to 6 weeks after internal cardioversion: group A (35 patients, oral diltiazem), group B (34 patients, oral amiodarone) and group C (37 patients, no antiarrhythmic drugs). Several electrophysiological parameters were assessed 5 min and 24 h after cardioversion. Results: Compared with controls, group B patients had significantly higher conversion rates (83% vs. 100%, p = 0.041) and a higher probability to maintain sinus rhythm (p = 0.037). Patients of group B had longer fibrillatory cycle length intervals than patients of group A and C (180 ± 18 ms vs. 161 ± 17 ms vs. 164 ± 19 ms, p = 0.001) and longer atrial effective refractory periods (211 ± 22 ms vs. 198 ± 16 ms vs. 194 ± 17 ms, p = 0.003) as assessed 5 min after conversion. Post-conversion density of supraventricular ectopics was significantly lower in group B compared to groups A and C (p = 0.001). Conclusions: Oral amiodarone increases conversion rates, prolongs fibrillatory cycle length and atrial effective refractory period and preserves sinus rhythm after cardioversion in persistent AF patients by suppressing the atrial ectopics that trigger AF.     

胺碘酮对阵发性心房颤动射频消融术后复发的影响

心房颤动（房颤）是临床上最常见的心律失常,虽然迂10年来房颤的导管消融发展迅速,消融方法日渐完善,但术后仍存在较高的复发率。近年的研究表明房颤消融术后与期应用抗心律失常药物可以降低早期的房颤复发率^[1],任能否降低房颤的远期复发率仍存在争议心^[2-3]。本研究的目创是探讨胺碘酮对阵发性房颤患者导管消融术后近期和远剪复发率的影响。     

Efficacy of amiodarone for preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation after cardioversion.

BACKGROUND: It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. METHOD AND RESULTS: The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30+/-11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2 months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). CONCLUSION: In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling.     

静脉注射胺碘酮转复阵发性心房颤动的临床观察

目的：观察静脉注射胺碘酮转复阵发性心房颤动（PAF）的疗效和安全性。方法：80例发作1～24h的PAF患者,随机分为两组。胺碘酮组（40例）：胺碘酮150mg静脉注射,继以1mg／min静脉泵入．维持6h,去乙酰毛花苷组（40例）：去乙酰毛花苷0．4mg静脉注射,2h后追加0．2mg。观察PAF转复情况,心率、QTe是期变化及副作用。结果：胺碘酮组复律29例（72％）,去乙酰毛花苷组复律18例（45％）,P〈0．05。复律时间分别为（215±58）min。（253±39）min．P〈0．05。未转复者心率分别下降26％和11％。P〈0．05。QTc间期两组复律前后比较差异无显著性。两组均无严重副作用。结论：静脉注射胺碘酮转复PAF有效且安全。     

Efficacy of amiodarone for the termination of persistent atrial fibrillation

The efficacy and safety of amiodarone in the conversion of persistent atrial fibrillation (AF) were investigated in a prospective, randomized, controlled study. Of 67 consecutive patients (32 men, mean age 64+/-9 years) with AF lasting >48 hours, 33 received amiodarone and 34 received placebo. Baseline clinical characteristics were similar in the 2 groups. Patients randomized to amiodarone received 300 mg intravenously for 1 hour and then 20 mg/kg for 24 hours. They were also given 600 mg/day orally, divided into 3 doses, for 1 week and thereafter 400 mg/day for 3 weeks. Patients randomized to placebo received an identical amount of saline IV over 24 hours and then oral placebo for 1 month. Conversion to sinus rhythm was achieved in 16 of the 33 patients (48.5%) who received amiodarone and in none of the 34 patients in the placebo group (p <0.001). None of the patients converted to sinus rhythm within the first 3 days. Those who converted had smaller atria than those who did not (diameter 41.9+/-7.2 vs 50.4+/-5.7 mm, p <0.001). Sex, age, baseline heart rate, left ventricular ejection fraction, and the duration of AF did not differ significantly between patients who converted and those who did not. No side effects requiring discontinuation of treatment were observed in either group. Amiodarone, administered both intravenously and orally, appears to be safe and effective in the termination of persistent AF. Left atrial diameter is the sole independent predictor of conversion.     

Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation

Background

Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort.

Methods

This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study.

Results

Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls (P <.0001). Overt hypothyroidism, TSH level >10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls (P <.001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH <0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P = .07).

Conclusions

Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case.     

Early recurrence of atrial fibrillation after ambulatory shock conversion

OBJECTIVES: We sought to gain insights into the early recurrence of atrial fibrillation (ERAF) after cardioversion shocks delivered by permanently implanted rhythm management systems. BACKGROUND: Several reports have characterized ERAF, but these reports used a limited definition and did not evaluate an association between clinical or device variables and ERAF. METHODS: A total of 144 patients with recurrent, drug-resistant, symptomatic atrial fibrillation (AF) underwent implantation of an atrial rhythm management system (Medtronic Jewel AF, Model 7250, Minneapolis, Minnesota). The device was programmed to deliver cardioversion shocks automatically and/or on patient command. The incidence of ERAF was evaluated after 1,092 successful shocks among 97 patients. Three different ERAF definitions were used: recurrence within 1 min, 1 h or 1 day. Multiple clinical and device variables were assessed for their relationship with ERAF. RESULTS: The per-patient incidences of ERAF were 44%, 61% and 70% for ERAF within 1 min, 1 h and 1 day, respectively. The per-episode incidences of ERAF were 17%, 30% and 43% for ERAF within 1 min, 1 h and 1 day, respectively. Variables that were independently associated with ERAF included AF duration <3 h before termination, more than one shock required to cardiovert and the absence of a previous myocardial infarction. The most potent variable was AF duration <3 h, associated with a threefold increase in the incidence of ERAF. CONCLUSIONS: Recurrence of AF early after ambulatory shock cardioversion is common. In this retrospective study, both clinical and device variables were predictive.     

阿托伐他汀钙在胺碘酮转复持续性心房颤动中的作用观察

目的探讨阿托伐他汀钙联合胺碘酮转复持续性心房颤动(简称房颤)及房颤复律后维持窦性心律的作用及其对血清炎症反应的影响。方法 68例持续性房颤患者,随机分为两组。对照组34例给予胺碘酮,治疗组34例给予胺碘酮和阿托伐他汀钙。两组均连续服药6个月,观察房颤转复后窦性心律维持率及转复前后血清高敏C反应蛋白(hs-CRP)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)变化。结果治疗组房颤转复率、窦性心律维持率均较对照组高(79.41%vs 61.76%,76.47%vs 55.88%,P均<0.05),对照组治疗前后hs-CRP、IL-6、TNF-α无变化(P>0.05),治疗组治疗后hs-CRP、IL-6、TNF-α明显降低(P<0.05)。结论阿托伐他汀钙可以降低房颤的复发,其机制可能与抗炎作用相关。     

胺碘酮与胺碘酮联合用药治疗心房纤颤疗效的比较

目的:观察单纯用药与联合用药对心房纤颤（房颤）治疗效果。方法: 选择119例房颤患者随机分为2组:单纯用药组54例,给予静脉胺碘酮150~300 mg后,继之以口服胺碘酮维持;联合用药组65例,使用极化液、硝酸甘油和小剂量利尿剂、胺碘酮,胺碘酮使用的剂量与方法同单纯用药组。观察两组房颤转复率和窦性维持率。结果: 联合用药组的房颤转复率较单纯组明显提高（80% vs. 94%,P＜0.05）,复律时间减少［（55±19） vs.(39±15） s,P＜0.05］,追踪复律半年后的维持率,联合用药组明显高于单纯用药组（81% vs. 95%,P＜0.05）。复查B超显示:联合用药后,左心房内经明显缩小,从［(46±6) mm减少到(42±6) mm,P＜0.05］,左心室舒张末期内径缩小,从(52±7) mm减少到(45±6) mm(P<0.05);而单纯用药组这两项指标均无明显改变。结论: 联合用药组较单纯用药组能明显提高对房颤患者的转复率和窦性维持率。     

Comparison of effectiveness of ranolazine plus amiodarone versus amiodarone alone for conversion of recent-onset atrial fibrillation

Ranolazine, an antianginal agent with antiarrhythmic properties, prevents atrial fibrillation (AF) in patients with acute coronary syndrome. In experimental models, the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF. Currently, the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown. This prospective randomized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF. We enrolled 51 consecutive patients with AF (<48-hour duration) eligible for pharmacologic cardioversion. Patients (33 men, 63 ± 8 years of age) were randomized to intravenous amiodarone for 24 hours (group A, n = 26) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of randomization (group A + R, n = 25). The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter. Conversion within 24 hours (primary end point) was achieved in 22 patients (88%) in group A + R versus 17 patients (65%) in group A (p = 0.056). Time to conversion was shorter in group A + R than in group A (9.8 ± 4.1 vs 14.6 ± 5.3 hours, p = 0.002). According to Cox regression analysis, left atrial diameter and A + R treatment were the only independent predictors of time to conversion (hazard ratio 5.35, 95% confidence interval 2.37 to 12.11, p <0.001; hazard ratio 0.81, 95% confidence interval 0.74 to 0.88, p <0.001, respectively). There were no proarrhythmic events in either group. In conclusion, addition of ranolazine to standard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF.     

胺碘酮对阵发性心房颤动射频消融术后复发的影响

目的探讨阵发性心房颤动(paroxysmal atrial fibrillation,PAF)射频消融术后应用胺碘酮对术后心房颤动(AF)复发的影响。方法收集2012-07~2014-12行射频消融术治疗且已达消融终点的PAF患者84例。根据随机数字表法将患者分为治疗组和对照组,每组42例。对照组在消融术后未使用抗心律失常药物治疗,治疗组在消融术后使用胺碘酮治疗,比较两者术后早期复发和晚期复发情况,以及术后不同时间点左心房内径(left atrial diameter,LAD)和左室射血分数(left ventricular ejection fraction,LVEF)的变化情况。结果术后第3个月随访时,治疗组心率为61~89(69.3±3.1)次/min,对照组心率为68~108(77.8±4.5)次/min,治疗组心率明显低于对照组(P0.01)。治疗组的早期复发率、晚期复发率均明显低于对照组(P0.05)。治疗组术后3个月、12个月时LAD明显小于对照组,LVEF水平明显高于对照组(P0.05)。结论对PAF患者,射频消融术后使用胺碘酮可预防AF的复发,逆转左心房的结构及电活动重塑,改善患者心功能,值得临床推广应用。     

On the possibility of amiodarone use in some cases of persistent atrial fibrillation

Aim of the study was to investigate mechanisms of amiodarone action on atrial and ventricular rhythm during persistent atrial fibrillation (PAF), and to assess efficacy of amiodarone as monotherapy or in combination with digoxin. Holter ECG monitoring and registration of high resolution ECG with construction of periodograms of ff waves and histograms of RR intervals (MATLAB 5.3 environment) were carried out in 34 patients (mean age 63.1+/-11.0 years) with PAF. Amiodarone (550.0+/-143.4 mg/day), digoxin (0.30+/-0.09 mg/day) with amiodarone (571.4+/-106.9 mg/day) were given for 21 days with recordings of high resolution ECG at baseline and on day 21. Long term therapy (1.7 years) with combination of digoxin 0.19+/- 0.07 mg/day) and amiodarone (254+/-82.0 mg/day) was controlled by Holter ECG monitoring. Monotherapy with amiodarone was not associated with significant lowering of heart rate (HR) (small er, Cyrillic=0.054) because of complex effect of amiodarone of HR: significant increase of period of ff waves (by 0.031+/-0.011 s), with facilitation of their conduction to ventricles combined with significant 0.10+/-0.08 s increment of minimal RR. Amiodarone combined with digoxin caused significantly lesser (by 0.009+/-0.017 s) enlargement of ff waves and significant lowering of HR (by 21.24+/-15.77 bpm) at the account of slowing of AV conduction (minimal RR increased by 0.12+/-0.08 s) and suppression of early RR peaks (0.28-0.46 s). The combination effectively suppressed tachysystolia resistant to other therapy (maximal HR 170-215 bpm) with significant lowering of mean (by 16.5+/-13.1 bpm) and maximal (by 43.3+/-35.6 s) HR, with suppression of ventricular extrasystoles in 83% of patients, and without significant lowering of minimal HR and appearance of pauses from 3 s. Level of thyrotrophic hormone rose from 2.4 to 5/9 IU/ml (p >0.05).     

持续性心房颤动环肺静脉消融术后随访及复发因素

目的探讨Lasso标测导管指导下环肺静脉消融术(CPVA)后心房颤动(简称房颤)早晚期复发的预测因素。方法收集持续性房颤CPVA术后患者的临床及电生理资料结合术后随访,进行多因素相关分析,了解各因素与术后房颤复发的相关性。结果共89例行CPVA术,早期复发房性心律失常29例(32.6%),其中房颤19例(21.3%),晚期共复发房颤29例(32.6%)。多因素回归分析提示最大P波时程(OR1.024,CI1.002～1.046,P=0.03)是房颤早期复发的独立预测因素;而对于房颤晚期复发来说,器质性心脏病(OR4.849,CI1.582～14.866,P=0.006)以及最大P波时程(OR1.048,CI1.017～1.080,P=0.002)是独立预测因素。结论持续性房颤CPVA术后患者,最大P波时程是早晚期复发的独立预测因素,器质性心脏病是晚期复发的独立预测因素。     

已达到消融终点的长程持续性心房颤动复发危险因素分析

目的：探讨已达到消融终点的长程持续性心房颤动（房颤）患者复发的危险因素。方法：纳入达到消融终点的长程持续性房颤患者256例,消融终点定义为双侧肺静脉电隔离,二尖瓣峡部和左心房顶部线性消融双向阻断且碎裂电位消失。根据随访结果将患者分为房颤复发组（n＝43）和无复发组（n＝213）。通过多因素 COX 回归分析探讨房颤复发的独立危险因素。结果：经过（19．5±3．6）个月随访,与无复发组相比,房颤复发组患者右心房内径较大,为（53．31±6．55）mm 对（48．74±5．87）mm;房颤持续时间较长,为（81．83±45．75）个月对（53．16±40．23）个月;左心房内径较大,为（49．85±6．82）mm 对（46．77±5．83）mm,P 均＜0．01。多因素 COX 回归分析发现,左心房内径增大（OR＝1．01,95％CI：1．01～1．28,P ＜0．05）,右心房内径增大（OR＝2．85,95％CI：1．15～7．03,P ＜0．05）、房颤持续时间延长（OR＝1．01,95％CI：1．01～1．02,P ＜0．05）是房颤复发的独立危险因素。结论：除左心房内径和房颤持续时间外,右心房内径增大也是已达到消融终点的长程持续性房颤复发的独立危险因素。