非抗心律失常药物防治心房颤动的研究进展

心房颤动(房颤)是临床中最常见的心律失常之一,可致心血管疾病高发病率和病死率。他汀类药物和肾素-血管紧张素-醛固酮系统抑制剂等非抗心律失常药物在房颤的上游防治中发挥了重要作用。本文就血管紧张素转换酶抑制剂、血管紧张素受体拮抗剂、醛固酮受体拮抗剂和他汀类药物等防治房颤的作用机制及临床应用研究进展进行综述。     

心律失常上游药物的治疗研究进展

心律失常是临床上最常见的疾病之一,是当今心脏疾病领域中的一大难题。无论是药物治疗还是非药物治疗,都有很多问题需要解决。近年来研究显示血管紧张素转换酶抑制剂（ACEI）、血管紧张素受体阻滞剂（ARB）、醛固酮受体拮抗剂、他汀类药物、不饱和脂肪酸等心律失常上游药物（upstream medical agents）均具有抗心律失常作用。     

心律失常上游药物的治疗研究进展

心律失常是临床上最常见的疾病之一,是当今心脏疾病领域中的一大难题.无论是药物治疗还是非药物治疗,都有很多问题需要解决.近年来研究显示血管紧张素转换酶抑制剂(ACEI)、血管紧张素受体阻滞剂(ARB)、醛固酮受体拮抗剂、他汀类药物、不饱和脂肪酸等心律失常上游药物(upstream medical agents)均具有抗心律失常作用.     

ACEI/ARB在心房颤动的预防治疗作用

心房颤动是临床上最常见的心律失常,并且很难治愈。目前,大家都把兴趣集中在针对发病机制的新治疗手段。近期研究提示,肾素-血管紧张素-醛固酮系统在心房颤动的发病机制中是一个非常重要的内分泌系统。因此,血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂都成为了预防心房颤动的新型药物。现对血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂在心房颤动治疗中所发挥的作用进行了讨论,并回顾了大量血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂在高危心房颤动人群（如心力衰竭、高血压、心肌梗死等）的临床研究。     

血管紧张素Ⅱ受体拮抗剂在心房颤动防治中的研究进展

心房颤动是临床上最常见的心律失常之一,抗心律失常药物因效果不佳且不良反应多,使其在心房颤动的防治中应用有限。血管紧张素Ⅱ通过促进心房纤维化,缩短心房有效不应期,延长房室传导,诱导细胞内Ca^2＋超负荷及炎症反应等,促进心房的电重构及组织重构,从而在心房颤动的发生和维持中起积极作用。越来越多的研究表明血管紧张素Ⅱ受体拮抗剂在心房颤动的防治中具有广泛作用。     

阻断肾素-血管紧张素系统——临床心房颤动防治的新靶点

抗心律失常药物在心房颤动(房颤)预防和治疗方面疗效差且有潜在的严重副作用,而很少涉及心律失常领域的血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB),却在某些高危人群的房颤防治中显示了有益的作用。我们就阻断肾素-血管紧张素系统(RAS)防治房颤及其可能的作用机     

肾素-血管紧张素系统阻断剂与心房颤动

心房颤动是临床最常见的心律失常之一,发病率呈增加趋势。心房电重构和结构重构是心房颤动维持和复发的主要机制,肾素-血管紧张素系统在心房重构中起重要作用。肾素-血管紧张素系统阻断剂（血管紧张素转化酶抑制剂和血管紧张素受体阻断剂）通过抑制心房不应期缩短和抗心房结构重构等作用抑制心房重构并减少心房颤动的发作。肾素-血管紧张素系统阻断剂影响心房结构和功能,为心房颤动的防治提供了一种新的选择。     

ACEI和ARB类药物在心房颤动治疗中的应用

心房颤动是临床最常见的心律失常之一.有研究表明肾素-血管紧张素系统的激活可能参与心房颤动的发生、维持和发展过程;血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体阻滞剂(ARB)可以在心房颤动的预防和治疗中发挥重要作用,本文对ACEI和ARB类药物在心房颤动治疗中的应用做一综述.     

心力衰竭患者心律失常的药物治疗

心力衰竭(简称心衰)患者易发各类心律失常,其中,以合并心房颤动(简称房颤)和室性心动过速(简称室速)为最常见。对于心衰并发心律失常的患者而言,胺碘酮和β受体阻滞剂是既有效、又安全的药物选择,Ⅰ类抗心律失常药不宜使用。其他非抗心律失常药物,如他汀类、血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体拮抗剂等,对心衰并发心律失常的患者也是大有裨益的。     

血管紧张素转换酶抑制剂与血管紧张素Ⅱ受体拮抗剂预防心律失常的研究进展

血管紧张素转换酶抑制剂(ACEI)及血管紧张素Ⅱ受体拮抗剂(ARBs)在心血管疾病中广泛应用,对心血管疾病的治疗及预防起着极其重要的作用。目前研究认为,ACEI及ARBs在心律失常的预防中也具有一定的作用,尤其在预防心房颤动方面研究较多,现就ACEI及ARBs在心律失常中的作用及其机制作一综述。     

Cost-Effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation

To determine whether treatment with antiarrhythmic drugs could be cost-effective in preventing thromboembolic events in patients with paroxysmal atrial fibrillation (AF), 4 groups of patients without prior thromboembolism were studied. Group A: 193 patients with paroxysmal AF receiving antiarrhythmic drugs, but not antiplatelets or warfarin; Group B: 228 patients with paroxysmal AF not receiving antiarrhythmics, antiplatelets or warfarin; Group C: 284 patients with chronic AF receiving warfarin; Group D: 394 patients with chronic AF not receiving antiplatelets or warfarin. Direct costs for treatment of AF were determined. During a follow-up period of 4.6 years, the prevalence of thromboembolic episodes was lower by 70% in Group A and by 47% in Group C than in each control group. To prevent one thromboembolic event annually with antiarrhythmic drugs in patients with paroxysmal AF, an extra cost of 6.16 million yen was required. This less favorable cost-effectiveness was mainly because of physician's preference for new antiarrhythmic drugs. In contrast, treatment with warfarin required an extra cost of 1.09 million yen to prevent one thromboembolic event annually in patients with chronic AF. Antiarrhythmic drugs are less cost-effective in preventing thromboembolic events in patients with paroxysmal AF when new, expensive drugs are preferentially selected.     

Electrophysiologic drug testing in prophylaxis of sporadic paroxysmal atrial fibrillation: Technique,application, and efficacy in severely symptomatic preexcitation patients

Electrophysiologic drug testing was performed in nine patients with severely symptomatic sporadic (2 to 13 [mean 4.2] attacks/24 months) paroxysmal atrial fibrillation (PAF). All patients had control inductions of sustained (> 30 seconds) AF by high right atrial stimulation, and attempted inductions following serial administration of drugs. Drugs tested were intravenous procainamide (1.0 to 1.5 gm) (five patients), intravenous propranolol (0.1 mg/kg) (three patients), oral quinidine (1.6 to 2.4 gm/day) (six patients), oral disopyramide (1.2 to 1.6 gm/day) (four patients), and oral aprindine (100 to 250 mg/day) (four patients). In all patients, one or more drugs prevented induction of sustained AF: procainamide (one patient), quinidine (five patients), disopyramide (four patients), and aprindine (four patients). All patients were treated with drugs which prevented induction of sustained AF and followed for 8 to 40 (mean 24) months. Seven patients tolerated their drugs: six had no AF and one had several short nonsustained attacks. Two patients did not tolerate their drugs: one had paroxysmal palpitation (on decreased aprindine dosage), and one had AF (while off of aprindine). In conclusion, electrophysiologic drug testing is feasible in patients with sporadic PAF. Inability to induce sustained AF following drug administration suggests successful prophylaxis of spontaneous PAF with the same drug.     

Drug-induced atrial fibrillation

Atrial fibrillation (AF) is the most common sustained rhythm disorder observed in clinical practice and predominantly associated with cardiovascular disorders such as coronary heart disease and hypertension. However, several classes of drugs may induce AF in patients without apparent heart disease or may precipitate the onset of AF in patients with preexisting heart disease. We reviewed the literature on drug-induced AF, using the PubMed/Medline and Micromedex databases and lateral references. Successively, we discuss the potential role in the onset of AF of cardiovascular drugs, respiratory system drugs, cytostatics, central nervous system drugs, genitourinary system drugs, and some miscellaneous agents. Drug-induced AF may play a role in only a minority of the patients presenting with AF. Nevertheless, it is important to recognize drugs or other agents as a potential cause, especially in the elderly, because increasing age is associated with multiple drug use and a high incidence of AF. This may contribute to timely diagnosis and management of drug-induced AF.     

Efficacy of catheter ablation of atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Although pulmonary vein (PV) antrum isolation is effective in curing atrial fibrillation (AF) in a variety of heart diseases, results in patients with hypertrophic obstructive cardiomyopathy (HOCM) have not been reported. OBJECTIVES: The purpose of this study was to report the results and outcome of PV antrum isolation in patients with AF and HOCM. METHODS: Data from patients with AF and HOCM who underwent PV antrum isolation between February 2002 and May 2004 were analyzed retrospectively. An intracardiac echocardiographic-guided ablation technique with an 8-mm-tip catheter was used in all patients. Patients were followed in the outpatient clinic at 3, 6, and 12 months after ablation. RESULTS: Twenty-seven patients with AF and HOCM (mean age 55 +/- 10 years) underwent PV antrum isolation. Mean AF duration was 5.4 +/- 3.6 years. AF was paroxysmal in 14 (52%), persistent in 9 (33%), and permanent in 4 (15%). During a mean follow-up of 341 +/- 237 days, 13 patients (48%) had AF recurrence. Of these patients, five maintained sinus rhythm (SR) with antiarrhythmic drugs, one patient remained in persistent AF, and seven patients underwent a second PV antrum isolation. After the second PV antrum isolation, five patients remained in SR, giving a final success rate of 70% (19/27). Two patients had recurrence after second PV antrum isolation; one maintained SR with antiarrhythmic drugs and one remained in persistent AF. CONCLUSION: Compared with previously reported results in patients with lone AF, AF recurrence after the first PV antrum isolation is higher in patients with HOCM. However, after repeated ablation procedures, long-term cure can be achieved in a sizable number of patients. PV antrum isolation is a feasible therapeutic option in patients with AF and HOCM.     

Right atrial overdrive pacing for prevention of symptomatic refractory atrial fibrillation.

AIMS: Our aim was to investigate whether right atrial overdrive pacing is effective for the prevention of atrial fibrillation (AF) in patients without bradyarrhythmias. METHODS AND RESULTS: Patients with symptomatic paroxysmal or persistent AF refractory to at least two Class I or III antiarrhythmic drugs and without bradyarrhythmias were included. Successful therapy was defined as the combination of (a) a reduction of AF burden with or without AAD use >75%, (b) total AF burden < or =5% per year, and (c) less than one electrical cardioversion per year. Lower rate was set at 70 b.p.m. Additional AF prevention and termination features were used in case of no success.After a median follow-up of 18 (10-55) months, therapy was effective in 19 of the 36 included patients (53%). In 74% of the successfully treated patients, additional antiarrhythmic drugs were used. In successfully treated patients, the AF burden was reduced from 15% (5-100%) to 0% (0-4%). Multivariate analysis showed that the concomitant use of a Class I or III antiarrhythmic drug, a lower AF burden before implantation and the use of an angiotensin converting enzyme inhibitor were predictors of successful therapy. CONCLUSION: Right atrial overdrive pacing in combination with antiarrhythmic drugs seems an attractive treatment option in drug refractory symptomatic AF patients.     

Right Atrial Compartmentalization Using Radiofrequency Catheter Ablation for Management of Patients with Refractory Atrial Fibrillation

INTRODUCTION: Atrial fibrillation (AF) is often refractory to antiarrhythmic drugs, and patients who are intolerant of AF may require the maze operation for cure. As a less invasive alternative, a catheter-based, right atrial compartmentalization procedure was evaluated. METHODS AND RESULTS: Twelve patients with AF refractory to Class I and III antiarrhythmic drugs were studied. Four linear right atrial radiofrequency ablations were performed, from superior to inferior vena cava in the posterior wall and interatrial septum, anteriorly from the superior vena cava to the tricuspid annulus through the appendage, and across the tricuspid valve-inferior vena cava isthmus. The radiofrequency catheter was dragged along each line three to four times, until the atrial electrogram amplitude decreased by 75% and there was bidirectional conduction block in the tricuspid valve-inferior vena cava isthmus. One complication occurred: sinus node dysfunction requiring a pacemaker. Eight patients were discharged from the hospital on no antiarrhythmic drugs, and four were discharged on previously ineffective antiarrhythmic drugs. Total duration of follow-up was 21.3 +/- 11.2 months. Four patients discharged on previously ineffective antiarrhythmic drugs had no recurrence of AF. One patient discharged off antiarrhythmic drugs had no recurrence of AF. Seven patients discharged off antiarrhythmic drugs had recurrent AF by 12.6 +/- 13.0 months (median 6, range 1 to 39); 3 of these 7 responded to previously ineffective antiarrhythmic drugs without further AF and 4 did not. Thus, 8 of 12 patients (67%) had suppression of AF after ablation on previously ineffective medication or no medication. CONCLUSION: Right atrial compartmentalization may alter the substrate for AF, thus improving the efficacy of previously ineffective antiarrhythmic drugs. Because it is relatively safe, it may be a reasonable adjunctive intervention to maintain sinus rhythm in patients with drug-refractory AF.     

Antiarrhythmic drugs management in patients with atrial fibrillation: the new guidelines

Antiarrhythmic drug therapy will continue to play an important role in the treatment of atrial fibrillation (AF). Pharmacological therapy is focused on AF symptom relief and on prevention of tachycardiomyopathy. The choice between the various anti-arrhythmic drugs available, either for rate or rhythm control, mainly depends on the underlying cardiac disease, type of AF and possible side-effects. New anti-arrhythmic drugs in the guidelines vernakalant and dronedarone are promising, but further research is required to explore their role in treatment of patients with AF. In this review, we will discuss the role of antiarrhythmic drugs in management of patients with AF according to the new AF guidelines of the European Society of Cardiology.     

Medical Management of Atrial Fibrillation: State of the Art

Predominantly a disease of advancing age, atrial fibrillation (AF) is the most common sustained arrhythmia. Its prevalence is rising as the proportion of elderly people in the population continues its inexorable rise. Without more effective therapeutic interventions, AF-related cardiovascular and cerebrovascular morbidity and mortality will also continue to rise. Antiarrhythmic drugs are an essential tool in the management of AF and may be used as premedication before cardioversion; together with cardioversion to help or assist cardioversion; or given afterward to prevent recurrence. If AF recurs after one or two cardioversions, then it is usual to adopt a rate control strategy; highly symptomatic patients who fail cardioversion may benefit from ablation therapy. We are already on the threshold of a large expansion in the use of ablation therapy, a strategy that has potential to deliver dramatic improvements in outcome. Not only can AF be cured by ablative therapy, but there is also evidence that it confers functional improvement as well. It will not, however, be appropriate for all AF patients and pharmacological therapies will continue to have an important place in the management of AF. The plethora of antiarrhythmic drugs currently available for the treatment of AF is a reflection that none is wholly satisfactory, each having limited efficacy combined with poor safety and tolerability. Improved class III antiarrhythmic agents, such as dronedarone; new classes of antiarrhythmic agents, such as atrial repolarization delaying agents; and upstream therapies dealing with substrate represent potential sources of new pharmacological therapies for AF.     

Insights into Mechanisms of Antiarrhythmic Drug Action From Experimental Models of Atrial Fibrillation

Antiarrhythmic Drugs in AF. Atrial fibrillation (AF) remains a challenge to medical therapy. Over the past several years, a variety of experimental models of AF have been developed. These have provided insights into mechanisms underlying AF and antiarrhythmic drug action against the arrhythmia. A variety of drugs effective against clinical AK, including flecainide. propafenone, procainamide, and sotalol, have been found to terminate experimental AF, All of these agents appear to act by prolonging the wavelength for atrial reentry at rapid rates, thereby increasing the size and decreasing the number of functional circuits maintaining the arrhythmia. While the ability to terminate AF is determined by refractoriness prolongation at rapid rates, refractoriness prolongation at slow rates (e.g., sinus rhythm) can prevent AF induction by premature beats. Thus, drugs with strong reverse use-dependence (like sotalol) may be much more effective in preventing than in terminating AF. Spacial heterogeneity in refractoriness is an important contributor to AF occurrence in some models, particularly vagal AF, and is reduced by some (but not all) drugs that terminate AF, New insights are being gained into mechanisms of electrical remodeling, which promotes AF maintenance when rapid atrial rates are maintained, such as during AF, This electrical remodeling may be an interesting novel target for therapy of AF, Insights into AF mechanisms obtained in experimental models of AF should help in the development of new and improved therapeutic approaches.     

Relation of early termination of persistent atrial fibrillation by cardioversion or drugs to ablation outcomes

Current ablation consensus documents define persistent atrial fibrillation (AF) as AF lasting >1 week to 1 year or AF requiring cardioversion or pharmacologic conversion in <1 week. These 2 persistent AF subgroups may have different clinical characteristics and ablation outcomes. We compared 179 patients whose persistent AF was always terminated in <1 week by cardioversion/drugs to 244 whose AF actually lasted >1 week to 1 year. Patients with AF termination in <1 week by cardioversion/drugs had smaller left atrial (LA) size (4.1 ± 0.6 vs 4.5 ± 0.7 cm, p <0.0001), a longer AF history (7.5 ± 7.5 vs 6.0 ± 7.2 years, p = 0.035), more failed drugs (1.6 ± 1.0 vs 1.3 ± 1.0, p = 0.004), lower body mass index (28.5 ± 5.5 vs 30.3 ± 5.5, p = 0.0008), and fewer cardiomyopathies (3.9% vs 11.1%, p = 0.01). Cox multivariate analysis showed that LA size (p = 0.02), female gender (p = 0.001), and coronary artery disease (p = 0.03) predict ablation failure. There was a linear relation between duration of longest AF episode and LA size (p = 0.0001). Longest AF episode duration was the only factor predicting LA size (p = 0.001). Kaplan-Meier analysis showed more patients with AF termination in <1 week by cardioversion/drugs were free of AF after ablation (p = 0.042) than those whose AF actually lasted >1 week to 1 year. Once AF lasted >1 week, duration up to 1 year did not affect ablation success. In conclusion, patients whose persistent AF is always terminated by drugs/cardioversion in <1 week have different clinical characteristics and better ablation outcomes than patients whose AF persists beyond 1 week. This suggests that maintaining sinus rhythm before ablation is beneficial and that the definition of AF2 may need revision.