Long-term efficacy and safety of very-low-dose amiodarone treatment for the maintenance of sinus rhythm in patients with chronic atrial fibrillation after successful direct-current cardioversion

Background Long-term maintenance of sinus rhythm after successful conversion of chronic atrial fibrillation （CAF）, often ameliorates patients＇ symptoms, reduces the risk of ischemic stroke and improves cardiovascular hemodynamics. This prospective study aims to evaluate the long-term efficacy and safety of very low-dose amiodarone （100 mg daily） for the maintenance of sinus rhythm after successful direct-current （DC） cardioversion in patients with CAF and rheumatic heart disease （RHD） post intervention. Methods This study was a randomized prospective trial. One day after successful DC cardioversion （remained normal sinus rhythm） in patients with CAF and RHD post intervention for more than six months and adequate anticoagulation, all were randomly administered either amiodarone 200 mg daily in group A or amiodarone 100 mg dally in group B. Results A total of 76 patients （40 men and 36 women） were examined from February 1998 to December 1999. The mean age of the patients was （664- 10） years, and the mean follow-up was （674-8） months （range 61 to 84 months）. Actuarial rates of the maintenance of sinus rhythm were similar in the two groups after 5 years of follow-up. Four patients （11%） in group A but none in group B experienced significant adverse effects that necessitated withdrawal of amiodarone. No death occurred during the study period. Conclusion A very low dose of amiodarone results in adequate long-term efficacy and is safe for maintaining sinus rhythm in patients with CAF and RHD post intervention after successful DC cardioversion.     

Triiodothyronine and amiodarone effects on β3-adrenoceptor density and lipolytic response to the β3-adrenergic agonist BRL 37344 in rat white adipocytes

Summary— The β-adrenergic effects of catecholamines are potentiated by thyroid hormones in adipose tissue. Amiodarone (AM) is structurally similar to thyroid hormones and was used to explore the mechanism of the triiodothyronine (T₃) effect on β-adrenergic receptors (β-ARs) in adipose tissue. AM decreases the expression of some T₃ sensitive genes in various tissues and antagonizes the effect of T₃ on its nuclear receptors. In this study, the T₃, AM and AM + T₃ effects on the β1- and β₃-AR density were assessed on rat white adipocytes by radioligand binding using [³H]CGP 12177 after characterization of these subtypes by displacement of [³H]CGP 12177 binding by isoproterenol, BRL 37344 and noradrenaline. BRL 37344 was used to study β₃-AR lipolysis. White adipocytes from hyperthyroid rats had increased responsiveness (E_max × 2) and sensitivity (+ 38%) to BRL 37344, while those given AM alone had decreased values. Moreover, AM antagonized the T₃ effect on lipolysis. The β₁-binding characteristics (receptor density [B_max]: 45 ± 4 fmol/mg of proteins; dissociation factor [K_d]: 0.96 ± 0.10 nM) were not modified by either compound. Finally, T₃ significantly increased β₃-AR density (587 ± 69 versus 363 ± 25 fmol/mg of proteins) and K_d (38 ± 2 versus 23 ± 3 nM), while AM alone had no effect and did not antagonize the T₃ effect on β₃-AR number. In conclusion, the hyperthyroid state in the rat potentiated the lipolytic response of white adipocytes to a specific β₃-agonist and increased the β₃-AR density without changing in β₁-AR number and affinity. Furthermore, the lack of antagonism between AM and T₃ on β₃-AR expression suggests that T₃ does not work directly on the β₃-AR gene. Moreover, AM induced a functional tissular hypothyroid-like effect and its antilipolytic effect probably occurred at a postreceptor level.     

Iohexol contrast medium induces QT prolongation in amiodarone patients

AIMS: Amiodarone is widely used in ventricular tachyarrhythmias and atrial fibrillation, known to prolong QT-intervals. Concurrent administration of drugs prolonging QT- time can induce life-threatening ventricular tachyarrhythmia. METHODS: QT-interval changes following use of Iohexol contrast-medium for coronarangiography were observed comparing 21 patients taking long-term amiodarone therapy with 21 controls not taking amiodarone or QT-prolonging drugs retrospectively. RESULTS: Concurrent use of Iohexol and amiodarone was associated with significant prolongation of QTc-interval (433, 95%CI: 419-448 ms vs. 480, 95%CI: 422-483 ms, P < 0.001) the day after coronarangiograpgy. 6/21 patients showed severe prolonged QTc-interval of >500 ms. CONCLUSION: Caution is advised until more is known about pro-arrhythmic effects of Iohexol.     

胺碘酮的肺毒性及其防治

胺碘酮属Ⅲ类抗心律失常药，用于室性心律失常、心房颤动等的预防治疗。长期用药发生不良反应的风险增加，其中以肺毒性最为常见，发生率为1％-17％，多在连续用药3～12月后出现间质性肺炎或过敏性肺炎。胺碘酮致肺毒性的机制尚不明确，可能为药物直接细胞毒性作用，过敏反应、炎性反应或免疫反应的结果；患者原有肺部疾病、药物剂量较大或使用时间过长与肺毒性相关。临床主要表现为干咳、呼吸困难、乏力、体重下降、发热等。胸片以肺实质和间质同时受累最为常见。应用胺碘酮后，出现新发症状或原症状加重，新出现的胸片异常或胸部病变加重，肺功能检查示CO或肺总量下降〉15％，应考虑为肺毒性反应。建议使用胺碘酮前进行利益／风险评价，长期用药应使用最小有效剂量，定期检测肺功能，以减少和及时发现肺毒性。一旦临床诊断为肺毒性，应及时减量和停药，多数患者停药后可缓解，严重者可短期使用皮质激素治疗。     

Amiodarone: What have we learned from clinical trials?

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This paper reviews clinical trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction trials include EMIAT and CAMIAT, both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In patients with congestive heart failure (CHF), amiodarone was associated with a neutral survival in CHF/STAT and improvement in survival in GESICA. In patients with nonsustained ventricular tachycardia, the MADIT trial demonstrated that therapy with an implantable cardioverter-defibrillator (ICD) improved survival compared with the antiarrhythmic drug arm in such patients, most of whom were taking amiodarone. In sustained VT/VF patients, the CASCADE trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared with other drugs guided by serial Holter or electrophysiologic studies. Several trials including AVID, CIDS, and CASH have demonstrated the superiority of ICD therapy compared with empiric amiodarone in improving overall survival. Clinical implications of these trials are discussed.     

Sudden death in dilated cardiomyopathy

The purpose of this review is to examine the potential contribution of arrhythmia to the occurrence of sudden death in dilated cardiomyopathy (DCM) and to discuss current treatment options. We performed a search of the MEDLINE database from 1985 to the present and the reference citations of selected articles pertaining to the prognostic significance, management, and pathophysiology of arrhythmias in DCM. A large proportion of patients with DCM die suddenly, most secondary to ventricular arrhythmia and a smaller proportion due to bradyarrhythmia. The presence and severity of ventricular ectopy may predict risk for sudden death, but the role of electrophysiologic study and signal-averaged electrocardiography in further risk stratifying patients remains uncertain. Abnormalities of the autonomic nervous system and renin-angiotensin-aldosterone axis appear to promote the occurrence of ventricular arrhythmias. Angiotensin-converting enzyme inhibitors improve overall mortality in congestive heart failure, and the use of direct angiotensin-receptor antagonists is currently being studied. In addition, beta-receptor antagonists appear to improve morbidity and may prove to improve mortality in heart failure as well. Other interventions still under investigation include amiodarone and the implantable cardioverter-defibrillator. The underlying pathophysiology of sudden death in DCM involves primarily ventricular tachyarrhythmia. Angiotensin-converting enzyme inhibitors remain a mainstay of improving overall mortality, while further study on the roles for newer drugs and devices is ongoing.     

胺碘酮所致大鼠肺毒性

为探讨胺碘酮所致肺毒性的发病机理,采用每日１ 次,连续５ ｄ 气管内注入０．１ ｍ Ｌ盐酸胺碘酮（１．２５ ｍ ｇ）生理盐水的方法,复制该病变的大鼠模型．该方法具有复制周期短,病变典型（出现明确的肺间质纤维化和肺泡腔内泡沫细胞聚集）及实验期间动物无死亡等优点． 此外采用原位杂交技术首次发现胺碘酮给药晚期肺巨噬细胞中肿瘤坏死因子αｍ ＲＮＡ 表达增多．     

小剂量胺碘酮预防老年人阵发性心房纤颤复发的疗效和安全性

目的 :探讨口服小剂量胺碘酮 (AD)预防老年人非瓣膜性心脏病阵发性房颤复发的疗效。方法 :40例老年阵发性房颤患者 ,给予AD6 0 0mg·d- 1 ,6d后渐减为维持量 5 0～ 1 0 0mg·d- 1 ,2 4h动态心电图观察评价其疗效。结果 :服药后 6月 ,1 2月和 2 4月 ,AD维持窦性心律的有效率分别为 90 0 % ,83 3 %和 72 7% ,因副作用停药者仅 5 % (2 /40 )。结论 :小剂量AD(5 0～ 1 0 0mg·d- 1 )可有效、安全的预防老年人阵发性房颤的复发。     

乙胺碘呋酮治疗心律失常60例疗效观察

本文报告乙胺碘呋酮(Amiodarone)治疗心律失常60例,总有效率为85％。分析了病因、年令、心律失常种类、用法、与疗效的关系。发现冠心病的疗效优于心肌炎。负荷量疗法较普通量疗法生效快,平均提前三天,而副作用未见增加。     

Probable early acute hepatitis with parenteral amiodarone

A patient with acute changes suggesting acute hepatitis after parenteral amiodarone administration is described. A 77-year-old man with previous myocardial infarction was admitted with chronic left heart failure and atrial tachycardia. Initial hepatic function tests were strictly normal. After therapy with parenteral amiodarone (2300 mg in 3 days) and other measures, signs of congestive heart failure disappeared; subsequently the patient developed jaundice, marked increase in serum transaminase levels and fall in prothrombin time, and histologic changes of severe centrilobular necrosis were observed in hepatic biopsy. Clinical, laboratory (absence of others markers of hepatic disease), and histological findings seem to rule out common causes of hepatic disease. Therefore, parenteral amiodarone was implicated as the cause of acute hepatitis in this patient. In addition, there were findings suggesting a possibly immunologically mediated mechanism.