The pharmacologic treatment of atrial fibrillation

The pharmacologic treatment of atrial fibrillation (AF) is aimed at controlling the ventricular response, restoring sinus rhythm, and preventing or delaying relapses. In the control of ventricular response, digitalis maintains a primary role when the arrhythmia is accompanied by heart failure. In ischemic, hypertensive, and degenerative (whose number is increasing at present) cardiopathies without evident ventricular dilatation, treatments with calcium antagonists (such as verapamil, gallopamil, or diltiazem) or beta-blocking agents must be preferred. In order to control the ventricular response in patients with chronic AF during physical activity, the association of digitalis with beta-blocking agents or calcium antagonists seems to provide satisfactory results. The drugs of the IC class, especially flecainide, represent a certain therapeutical progress in the restoration of sinus rhythm in the treatment of paroxysmal atrial fibrillation affecting subjects without evident alterations of ventricular function, particularly in subjects with Wolff-Parkinson-White syndrome, with forms of vagal origin, or with atrial fibrillation alone. A therapeutic combination of digitalis and quinidine may produce resolution of the arrhythmia in the presence of altered ventricular function or when AF is of an uncertain onset. In patients with hypertensive, ischemic, and/or degenerative cardiopathy without evident ventricular or advanced heart failure, the verapamil-quinidine association may also be effective and even quicker. The combination of drugs of the I and III class for restoration of the sinus rhythm in particularly resistant forms of AF without evident structural heart alterations is promising but must be verified in a greater number of patients. In the prevention of relapses amiodarone appears to have the widest spectrum of advantages from an electrophysiologic point of view; however, because of its many side effects, amiodarone represents a late therapeutical choice. The promising results obtained with flecainide are disputed by the results of the CAST, which limit the possibilities of using this drug to a low number of cases (W.P.W. syndrome, AF of vagal origin, atrial fibrillation alone). In the past, quinidine and disopyramide have been the drugs most widely used in the prophylaxis of AF. These drugs have a similar efficacy, and both of them provided some positive results. However, because of untoward side effects (especially for quinidine) during chronic treatment, the use of these drugs has been questioned. Perhaps in the majority of patients, the less dangerous therapeutic choice after the termination of the fibrillation is a combination of drugs slowly down AV node activity (digitalis or calcium antagonists and beta blockers) with class IA antiarrhythmics.     

Efficacy of intravenous amiodarone in the management of paroxysmal or new atrial fibrillation with fast ventricular response

We tested the efficacy of intravenous amiodarone (5 mg/kg) in slowing ventricular response and/or restoring sinus rhythm in 26 patients with paroxysmal or new atrial fibrillation with fast ventricular response. There were 16 men and 10 women with ages ranging from 35 to 84 years, mean 63 years. Intravenous amiodarone initially slowed the ventricular response in all patients from 143 +/- 27 to 96 +/- 10 beats/min (P less than 0.001). Twelve patients (46%) reverted to sinus rhythm within the first 30 min (range 5 to 30 min, mean 14 +/- 9 min). One patient reverted to atrial flutter after 10 min and 40 min later to sinus rhythm. Six patients (23%) converted to sinus rhythm after 2 to 8 hr and in these 6 cases, the initial slowing in ventricular response obtained with amiodarone persisted until conversion. Seven patients (27%) did not convert to sinus rhythm following amiodarone administration and they required further medical therapy to slow the ventricular response and/or to convert to sinus rhythm. No serious side effects from drug administration were noted. Intravenous amiodarone appears as a highly effective medication in the conversion or control of new onset atrial fibrillation with fast ventricular response.     

小剂量胺碘酮联合倍他乐克在肥厚型心肌病伴恶性室性心律失常治疗中的应用研究

目的探讨和分析小剂量胺碘酮联合倍他乐克治疗肥厚型心肌病伴恶性室性心律失常治疗中的临床效果。方法将94例肥厚型心肌病伴恶性室性心律失常患者按照住院时间先后顺序分组为对照组和观察组;对照组:采用倍他乐克治疗;观察组:采用小剂量胺碘酮联合倍他乐克治疗。对两组患者进行为期6~12个月随访。结果观察组和对照组的治疗有效率分别为95.7%(45/47)、80.9%(38/47)。除QT间期最大值以外,两组心电图指标和LVEF治疗后均较治疗前显著改善(P0.05),观察组治疗后心率和QT间期最小值以及QT散度、LVEF、再住院率、猝死率等方面均优于对照组(P0.05)。治疗和随访期间均没有发现明显性不良反应。结论采用小剂量胺碘酮联合倍他乐克治疗肥厚型心肌病伴恶性室性心律失常,可有效地改善患者的临床症状,效果明确。     

Efficacy and safety of ibutilide for cardioversion of atrial flutter and fibrillation in patients receiving amiodarone or propafenone

AIM: The effectiveness and safety of ibutilide (IB) use in patients receiving amiodarone or propafenone for atrial flutter (AFL) and atrial fibrillation (AF) were compared to IB alone. METHODS AND RESULTS: In 104 consecutive patients with AF (65%) or AFL (35%), receiving amiodarone (n = 46), propafenone (n = 30), or no specific antiarrhythmic drug (n = 28), IB was given for cardioversion. Fifteen patients in amiodarone group were loaded with 1.2 g intravenously before IB administration. The mean duration of arrhythmia episode was 23 +/- 65 days, while 85% of patients had structural heart disease. The left ventricle ejection fraction was 57 +/- 10% and the left atrium size was 4.2 +/- 0.6 cm. The conversion efficacy did not differ among groups (62% for amiodarone vs 55% for propafenone vs 64% for IB alone). The QTc intervals were significantly prolonged, at 10 minutes and 30 minutes after IB administration, in amiodarone group (from 449 +/- 88 to 496 +/- 92 ms, 508 +/- 52 ms; P = 0.001) and in the group where IB was used alone (from 434 +/- 45 to 517 +/- 74 ms, 492 +/- 65 ms; P < 0.001), while it remained unchanged in propafenone group (from 464 +/- 52 to 471 +/- 80 ms, 489 +/- 93 ms; P = 0.536). The only predictor of conversion was the presence of AFL (P = 0.009). Five patients developed ventricular tachycardias after IB administration (two in propafenone, one in amiodarone, and two in IB group). CONCLUSIONS: The use of IB in patients receiving amiodarone or propafenone for AFL or AF is equally effective and safe as the use of IB alone. The presence of AFL is the stronger predictor factor for cardioversion.     

Amiodarone and Bretylium in the Treatment of Hypothermic Ventricular Fibrillation in a Canine Model

Refractory ventricular fibrillation (VF) is a complication of severe hypothermia. Despite mixed experimental data, some authors view bretylium as the drug of choice in hypothermic VF. Bretylium was removed from Advanced Cardiac Life Support guidelines, and, to date, efficacy of amiodarone in hypothermia is unknown. OBJECTIVES: To compare defibrillation rates from hypothermic VF after drug therapy with amiodarone, bretylium, and placebo. METHODS: This was a randomized, blinded, and placebo-controlled laboratory experiment. Thirty anesthetized dogs were mechanically ventilated and instrumented to monitor coronary perfusion pressure (CPP), rectal core temperature, and electrocardiogram (ECG). Animals were cooled to 22 degrees C or the onset of spontaneous VF. Ventricular fibrillation was induced as needed with a transthoracic AC current. Cardiopulmonary resuscitation (CPR) was initiated and animals were randomized (n = 10 each group) to receive amiodarone 10 mg/kg (A), bretylium 5 mg/kg (B), or placebo (P) intravenously. CPR was continued while monitoring for chemical defibrillation. Rewarming was limited to removal from the cold environment. After 10 minutes, up to three escalating defibrillatory shocks were administered. Hemodynamic monitoring continued after resuscitation. Return of spontaneous circulation (ROSC) was defined as a sustainable ECG rhythm generating a corresponding arterial pressure tracing lasting a minimum of 15 minutes. Sample size permitted 80% power to detect a 60% difference in conversion rate between groups. RESULTS: CPR was adequate based on CPP > 15 mm Hg in all animals. Mean (+/-SD) CPP was 35.3 +/- 18.8 mm Hg with an overall lower trend in the amiodarone group (p = 0.06). Baseline variables were similar between groups. No instance of chemical defibrillation was noted. There was no significant difference in ROSC rates between groups. Resuscitation rates were: amiodarone = 1/10, bretylium = 4/10, and placebo = 3/10 (p = 0.45). CONCLUSIONS: In this model of severe hypothermic VF, neither amiodarone nor bretylium was significantly better than placebo in improving the resuscitation rate.     

Amiodarone-related pulmonary mass and unique membranous glomerulonephritis in a patient with valvular heart disease: Diagnostic pitfall and new findings

Amiodarone is an anti-arrhythmic drug for life-threatening tachycardia, but various adverse effects have been reported. Reported herein is an autopsy case of valvular heart disease, in a patient who developed a lung mass (1.5 cm in diameter) and proteinuria (2.76 g/day) after treatment with amiodarone for a long time. The lung mass was highly suspected to be lung cancer on CT and positron emission tomography, but histologically the lesion was composed of lymphoplasmacytic infiltrates in alveolar walls and intra-alveolar accumulation of foamy macrophages containing characteristic myelinoid bodies, indicating that it was an amiodarone-related lesion. In addition, the lung tissue had unevenly distributed hemosiderin deposition, and abnormally tortuous capillaries were seen in the mass and in heavily hemosiderotic lung portions outside the mass. In the kidneys, glomeruli had membrane spikes, prominent swelling of podocytes and subepithelial deposits, which were sometimes large and hump-like. Autoimmune diseases, viral hepatitis, malignant neoplasms or other diseases with a known relationship to membranous glomerulonephritis were not found. The present case highlights the possibility that differential diagnosis between an amiodarone-related pulmonary lesion and a neoplasm can be very difficult radiologically, and suggests that membranous glomerulonephritis might be another possible complication of amiodarone treatment.     

胺碘酮对心脏瓣膜置换患者华法林初始服药1周内抗凝效果的研究

 目的 在心脏瓣膜置换患者中研究胺碘酮对华法林初始服药1周内抗凝效果的影响。方法 在单独应用华法林的心脏瓣膜置换患者(n=200)及合并使用胺碘酮的心脏瓣膜置换患者(n=54)中,比较术后前5 d华法林累积剂量,术后第6日能否进入治疗窗及术后首次进入治疗窗时间的差异。结果 合并使用胺碘酮患者术后前5 d华法林累积剂量低于单独服用华法林患者;合并使用胺碘酮不影响术后第6日进入治疗窗及国际标准化比值（INR）值术后首次进入治疗窗的时间。结论 合并使用胺碘酮不影响心脏瓣膜置换患者华法林初始服药1周内的抗凝效果。     

INTESTINAL ABSORPTION KINETICS OF AMIODARONE IN RAT SMALL INTESTINE

Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic effects. These seem to be related, at least in part, to the pharmacokinetics of the drug and particularly to some features of its gastrointestinal absorption process. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes, but its low aqueous solubility can act as the rate limiting step for absorption, making the process erratic and variable. In order to gain an insight into the intestinal absorption mechanism of the drug and detect possible non-linearities, a series of experiments using a classical rat gut in situ preparation were carried out with three amiodarone hydrochloride solutions (10, 75, and 200 μg mL⁻¹). A synthetic non-ionic surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a rapid, sensitive technique that was validated. The amiodarone first-order absorption rate constants obtained in these conditions were similar. No significant differences between k_a values were found. Amiodarone absorption was clearly identified as a passive diffusion process. © 1997 John Wiley & Sons, Ltd.     

参松养心胶囊联合胺碘酮治疗室性早搏疗效观察

目的：观察参松养心胶囊与胺碘酮联合用药治疗室性早搏的临床疗效。方法：将120例患者随机分为两组,每组60例。治疗组采用参松养心胶囊与胺碘酮联合治疗,对照组采用胺碘酮治疗。结果：治疗组总有效率91．67％,对照组总有效率78．33％。结论：参松养心胶囊联合胺碘酮治疗室性早搏疗效显著。     

基于FAERS的胺碘酮相关失明不良事件信号挖掘研究

目的 基于FAERS对胺碘酮相关失明药物不良事件(adverse drug event,ADE)进行信号挖掘,探索相关失明ADE的发生特点以及胺碘酮与相关失明ADE的相关性。方法 提取FAERS 2016年第1季度-2021年第4季度共24个季度的胺碘酮相关失明ADE报告数据,利用报告比值比法和综合标准法进行数据挖掘。得到有效信号后,再利用MedDRA规范进行汉化及系统归类。结果 获得胺碘酮报告数39 166个,胺碘酮相关失明ADE报告503个,其中失明、单侧盲、黑朦、一过性黑朦4个首选语运用2种方法均提示生成可疑信号。在503份患者报告中,男性所占比例(64.41%)高于女性(31.22%),在已知年龄的患者中,年龄主要集中在 ≥ 65岁(6.16%)。报告人员以律师和消费者为主90.46%,医务人员占比较低;除给药途径未知的患者,其余所有患者给药途径为口服(66.80%)。胺碘酮相关失明ADE的中位发病时间为692 d(四分位间距422.5~1 045.75 d);占比最高的患者结局为其他严重的医疗事件,报告病例279例(55.47%),患者结局为死亡的报告病例73例(14.51%),居第3位。结论 需重视胺碘酮的失明风险,重点关注男性、>65岁老人、给药途径为口服的患者,加强用药前的眼科评估及用药中、用药后的眼部监测,及时诊断和治疗可防止相关失明ADE的发生。