The renin-angiotensin system: a therapeutic target in atrial fibrillation

There is growing evidence to suggest a role for the renin-angiotensin system (RAS) in the pathogenesis of atrial fibrillation (AF). Experimental animal data suggest RAS-dependent mechanisms for the development of a structural and electrophysiologic substrate for AF. This is consistent with clinical data demonstrating the effectiveness of RAS blockade in preventing new-onset or recurrent AF in a variety of patient populations including patients with hypertension and left ventricular hypertrophy, congestive heart failure, and those undergoing electrical cardioversion for AF. This review summarizes experimental and clinical evidence to date relating to the role of RAS in the pathogenesis of AF, and the efficacy of its inhibition in managing this common arrhythmia.     

Atrial fibrillation and renin-angiotensin system

Many recent mega-trials regarding atrial fibrillation have failed to prove the efficacy of antiarrhythmic drugs to improve the mortality and morbidity of patients with atrial fibrillation. Meanwhile, the upstream therapy of atrial fibrillation, the management of many components that lead to atrial fibrillation, has been paid much attention to, because its target would be the causes of atrial fibrillation itself. Among many upstream therapies, the blockade of the renin-angiotensin system would be promising from basic and clinical viewpoints, and also from rhythm management and stroke prevention.     

Prevention of atrial fibrillation by way of abrogation of the renin-angiotensin system: a systematic review and meta-analysis

The renin-angiotensin-aldosterone system (RAAS) has emerged as an important hormonal system in the initiation and pathogenesis of atrial fibrillation (AF). Therefore, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are emerging as novel drugs for the prevention of AF. A meta-analysis of 11 randomized, controlled, parallel-design clinical trials evaluating effect of ACEIs or ARBs on the development of AF was performed. Treatment with ACEIs or ARBs reduced the relative risk (RR) of AF in patients with hypertension by 23% [RR 0.769, P < 0.001, 95% confidence interval (CI) 0.686-0.862] and by 11% in patients after myocardial infarction (RR 0.898, P < 0.05, 95% CI 0.814-0.992). Reduction in AF was greatest in patients after electrical cardioversion (RR 0.491, P < 0.001, 95% CI 0.334-0.720) and in patients with heart failure (RR 0.684, P < 0.001, 95% CI 0.594-0.787). Overall, inhibition of the RAAS reduced the RR of AF by 19% (RR 0.810, P < 0.001, 95% CI 0.759-0.865).     

New anticoagulation drugs for atrial fibrillation

Atrial fibrillation (AF) confers an increased risk of ischemic stroke or thromboembolism that is reduced by long-term oral anticoagulant therapy. Until recently, the latter has typically been one from the vitamin K antagonist (VKA) class of drugs. Although highly effective, VKAs have limitations, and their use is challenging for both patients and clinicians. A new generation of oral anticoagulant drugs is emerging, including several drugs that appear to be viable alternatives to VKAs in AF patients.     

New antiarrhythmic treatment of atrial fibrillation

Antiarrhythmic pharmaceutical development for the treatment of atrial fibrillation (AF) is moving in several directions. The efficacy of existing drugs, such as carvedilol, for rate control and, possibly, suppression of AF, is more appreciated. Efforts are being made to modify existing agents, such as amiodarone, in an attempt to ameliorate safety and adverse effect concerns. This has resulted in promising data from the deiodinated amiodarone analog, dronedarone, and further work with celivarone and ATI-2042. In an attempt to minimize ventricular proarrhythmia, atrial selective drugs, such as intravenous vernakalant, have demonstrated efficacy in terminating AF in addition to promising data in suppression recurrences when used orally. Several other atrial selective drugs are being developed by multiple manufacturers. Other novel therapeutic mechanisms, such as drugs that enhance GAP junction conduction, are being developed to achieve more effective drug therapy than is offered by existing compounds. Finally, nonantiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, high-mobility group coenzyme A enzyme inhibitors and omega-3 fatty acids/fish oil, appear to have a role in suppressing AF in certain patient subtypes. Future studies will clarify the role of these drugs in treating AF.     

New antiarrhythmic treatment of atrial fibrillation

Antiarrhythmic pharmaceutical development for the treatment of atrial fibrillation (AF) is moving in several directions. The efficacy of existing drugs, such as carvedilol, for rate control and, possibly, suppression of AF, is more appreciated. Efforts are being made to modify existing agents, such as amiodarone, in an attempt to ameliorate safety and adverse effect concerns. This has resulted in promising data from the deiodinated amiodarone analog, dronedarone, and further work with celivarone and ATI-2042. In an attempt to minimize ventricular proarrhythmia, atrial selective drugs, such as intravenous vernakalant, have demonstrated efficacy in terminating AF in addition to promising data in suppression recurrences when used orally. Several other atrial selective drugs are being developed by multiple manufacturers. Other novel therapeutic mechanisms, such as drugs that enhance GAP junction conduction, are being developed to achieve more effective drug therapy than is offered by existing compounds. Finally, nonantiarrhythmic drugs, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, high-mobility group coenzyme A enzyme inhibitors and omega-3 fatty acids/fish oil, appear to have a role in suppressing AF in certain patient subtypes. Future studies will clarify the role of these drugs in treating AF.     

EnsiteNavX标测系统指导下环肺静脉左心房线性消融治疗心房颤动

目的 探讨EnsiteNavX标测系统指导下环肺静脉左房线性消融电隔离治疗心房颤动的疗效.方法 阵发性心房颤动14例和持续性心房颤动3例,采用EnsiteNavX标测系统进行环肺静脉左房线性消融.消融终点为肺静脉电隔离.结果 17例患者均达到消融终点;手术时间(226.1±36.2)min、X线曝光时间(41.3 ±12.8)min、放电时间(61.9±15.4)min.术后2例复发,1例再次消融成功,1例拒绝再次手术;随访3～26个月,14例(82.3%)无心房颤动发作;3例(17.7%)有心房颤动复发,但发作次数及时间均较术前明显减少,用胺碘酮治疗可控制(术前胺碘酮治疗无效).术中及随访期间无任何与操作相关的并发症.结论 Ensite NavX标测系统指导下环肺静脉左房线性消融治疗心房颤动有效、安全.     

New developments in anticoagulation therapy for Ione atrial fibrillation

Lone atrial fibrillation is a major health problem for elderly patients with cardiovascular risk factors as hypertension, congestive heart failure or previous myocardial infarction. The increased stroke rate of these patients is significantly reduced by oral anticoagulation (target: INR 2-3) and less effective by acetylsalicylic acid at a dose of 325 mg/d. As an alternative to the vitamin K-antagonistic anticoagulants currently the SPORTIF trial program is performed investigating the safety and efficacy of the oral direct thrombin inhibitor ximelagatran. Recent data derived from a dose-finding study and its open label continuous follow-up period are very encouraging with regard to the low incidence of bleeding complications and ximelagatran's clinical efficacy for the prevention of thromboembolic events. Large confirmatory trials engaging about 3000 patients each are under way in Europe as an open-label trial and the United Staates as a double blind trial. Results are being expected for the end of year 2002. These data will clarify the role of ximelagatran for the prevention of thromboembolic events in patients with lone atrial fibrillation and may give us an insight into a new standard drug regimen for stroke prevention in high risk patients.     

Renin-angiotensin system blocker use may be associated with suppression of atrial fibrillation recurrence after pulmonary vein isolation

Introduction: An additional approach may be essential to reduce recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI). We examined the efficacy of renin‐angiotensin system blockers (RAS‐B) in suppressing AF recurrences after PVI. Methods and Results: We retrospectively studied 264 consecutive patients (195 male, median age: 63 years) who underwent successful PVI of paroxysmal (n = 94) or persistent AF (n = 170). RAS‐B treatment was performed in 145 patients (angiotensin‐converting enzyme inhibitors; n = 13, angiotensin receptor blockers; n = 129, both; n = 3). Echocardiography was performed before and 3 months after the ablation to examine the occurrence of left atrial structural reverse remodeling (LA‐RR). After a median follow‐up of 195 (interquartile range: 95–316) days, AF recurred in 51 (19.3%) patients. A Cox regression analysis revealed that AF recurrence was significantly lower in the patients with RAS‐B than in those without (hazard ratio [HR] = 0.41 [95% confidence interval (CI): 0.23–0.71], P = 0.002). After a multivariate adjustment for potential confounders, the use of RAS‐B (HR = 0.39 [95% CI: 0.19–0.77], P = 0.007) and type of AF (HR = 0.30 [95% CI: 0.13–0.66], P = 0.003) were the independent predictors for AF recurrence during the entire follow‐up. Although effect of RAS‐B was not significant during the early follow‐up (<3 month), it was the only independent predictor during the late follow‐up (>3 months) (HR = 0.21 [95% CI: 0.08–0.53], P = 0.001). There were no significant differences in LA‐RR occurrence regarding RAS‐B medication. The use of RAS‐B was an independent predictor of late AF recurrences irrespective of an early LA‐RR occurrence. Conclusions: Treatment with RAS‐B significantly reduced the AF recurrence after PVI. This benefit became more prominent 3 months after the PVI. (PACE 2011; 34:296–303)     

New anticoagulants for the prevention of stroke in atrial fibrillation

Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter‐individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE‐LY) achieved an impressive reduction in stroke and non‐central nervous system (non‐CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non‐CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance.     

Surgery for atrial fibrillation

•

ATRIAL FIBRILLATION (AF) is the most common sustained disturbance of cardiac rhythm, affecting an estimated 2.3 million people in North America and 4.5 million people in the European Union.

•

ALTHOUGH AF IS ASSOCIATED with significant morbidity, mortality, and increased health care costs, more-precise and less-invasive surgical ablation procedures have been developed. Specific cardiac sites emitting the aberrant, premature electrical signals that induce AF are ablated, which results in excellent cure rates and allows normal sinus rhythm to resume.

•

THESE PROCEDURES can be performed with or without the use of cardiopulmonary bypass, through either traditional sternotomy or minimally invasive thoracotomy incisions. AORN J 86 (July 2007) 23-40. © AORN, Inc, 2007.

     

聚焦解决护理模式在房颤患者华法林治疗管理健康教育中的应用

目的：探讨聚焦解决护理模式在房颤患者华法林治疗管理健康教育中的应用。方法对100例住院房颤患者的服药依从性、监测国际标准化比值依从性、国际标准化比值达标率、并发症情况及再次栓塞事件发生率进行比较分析。结果健康教育后研究组患者心房颤动华法林抗凝自我护理知识知晓率及华法林抗凝同意率显著高于对照组（P＜0．05）,心房颤动抗凝管理量表知晓率显著高于对照组（P＜0．01）,服药依从性、监测国际标准化比值依从性、国际标准化比值达标率均显著优于对照组（P＜0．01）,出血并发症及再次栓塞事件均显著少于对照组（P＜0．05或0．01）。结论聚焦解决护理模式可有效提高房颤患者华法林抗凝自我管理能力,提高治疗依从性。     

A novel implantable cardiac telemetry system for studying atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Most in vivo experimental research on AF is performed in a surgical setting, on animals instrumented by external devices, or using commercial implantable pacemakers. This paper describes a novel implantable cardiac telemetry system, which allows the study of AF remotely in conscious and ambulatory animals over a few month period. To validate this concept, the system was built and implanted in a sheep for 3 months. During this period, the system was used to deliver chronic rapid atrial pacing for AF induction, and to record and measure atrial electrograms and atrial effective refractory period (AERP) daily. During the course of AF induction the AERP decreased, confirming the progression of the electrical remodeling process in the atria. Episodes of paroxysmal AF were successfully induced in the animal. Burst pacing therapy was delivered with the system, however, no AF termination was observed. Result shows that this telemetry-based pacing and monitoring system can be used to study AF in a conscious animal non-invasively for an extended period of time, making this system a unique research tool.     

Combination pharmacological cardioversion of permanent atrial fibrillation in post-prosthetic mitral valve replacement outpatients: a novel approach for the treatment of atrial fibrillation

This study explored the efficacy and safety of combination pharmacological cardioversion of permanent atrial fibrillation in outpatients following prosthetic mitral valve replacement. The study group comprised 99 outpatients who were randomly divided into two groups. In group 1 (n = 50), only ventricular heart rate was controlled. In group 2 (n = 49), combination pharmacological cardioversion therapy with low-dose oral amiodarone (2 mg/kg), captopril (0.25 mg/kg) and simvastatin (0.3 mg/kg) was administered daily. During 12 months of serial pharmacological treatment, the cardioversion rate was 6% for group 1 and 39% for group 2; the likelihood of cardioversion differed significantly between the two groups. In group 2, one patient developed severe pruritus that necessitated withdrawal from the study and six patients ceased captopril treatment after contracting a persistent cough. In summary, combination pharmacological cardioversion was found to be effective and safe in outpatients who had undergone prosthetic mitral valve replacement.     

Screening for undiagnosed atrial fibrillation

Introduction: Atrial fibrillation (AF) is a condition of global importance, and it is associated with significant morbidity, mortality, and healthcare costs. A considerable proportion of patients with AF are asymptomatic, and stroke may be the first clinical manifestation of their AF diagnosis. AF screening provides an opportunity to identify patients with undetected AF prior to suffering a devastating complication.

Areas covered: This review will provide a rationale for AF screening; summarize AF screening methods, studies, and economic analyses; evaluate AF as a condition meeting criteria for population screening; and discuss potential drawbacks.

Expert commentary: While AF screening is simple, low risk, and, in most cases, low cost, additional research is needed validating new technologies and devices; defining strategies for linking screening with initiation of oral anticoagulation therapy and determining whether AF screening ultimately reduces stroke and stroke-related complications and costs.