Pharmacological approaches in the treatment of atrial fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial cardiovascular morbidity and mortality. The arrhythmia can be initiated and/or maintained by rapidly firing foci, single- and multiple-circuit reentry. Once initiated, AF alters atrial electrical and structural properties (atrial remodeling) in a way that promotes its own maintenance and recurrence and may alter the response to antiarrhythmic drugs. Thus, initial episodes of paroxysmal (self-terminating) AF lengthens to the point where the arrhythmia becomes persistent (requires cardioversion to restore sinus rhythm) and permanent. AF usually requires a trigger for initiation and a favorable electrophysiological and/or anatomical substrate for maintenance. The substrate includes both cardiovascular (coronary artery disease, valvular heart disease, heart failure, hypertension, dilated cardiomyopathy) and non cardiovascular diseases (thyrotoxicosis, pulmonary diseases). Accordingly, the initial step in patients with AF requires a careful assessment of symptoms and identification of underlying reversible triggers and potentially modifiable underlying structural substrate and treat them aggressively. In contrast to other cardiac arrhythmias, antiarrhythmic drugs (ADs) are the mainstay of therapy. Long-term treatment of AF is directed to restore and maintain the sinus rhythm with class I and III ADs (rhythm-control) or to allow AF to persist and ensure that the ventricular rate is controlled (rate-control) with atrioventricular nodal blocking drugs (digoxin, beta-blockers, verapamil, diltiazem) and prevent thromboembolic complications with anticoagulants. However, the long-term efficacy of ADs for preventing AF recurrence is far from ideal, because of limited efficacy (AF recurs in at least one-half of the patients) and potential side effects, particularly proarrhythmia. Thus, the choice of the appropriate AD will depend on the temporal pattern of the arrhythmia, the presence of associated diseases, easy of administration and adverse effects profile, particularly the risk of proarrhythmia. The recent finding that angiotensin converting enzyme inhibitors and beta-blockers reduce the incidence of AF in patients post myocardial infarction with left ventricular dysfunction confirmed the importance of targeting the underlying arrhythmogenic substrate. This review focuses on the mechanisms underlying AF and the mechanism of action and the efficacy and safety profile of the ADs used in the treatment of atrial fibrillation. The advantages and disadvantages of rhythm and rate control, the role pill in a pocket concept and the role of the new ADs are dicussed.     

Current Management of Symptomatic Atrial Fibrillation

Atrial fibrillation (AF) is the most commonly encountered sustained arrhythmia. Heart rate control, reduction of symptoms, and prevention of embolism are major goals of treatment. Whether the strategy of cardioversion with subsequent maintenance of sinus rhythm has an advantage over heart rate control is under active investigation. Digoxin, non-dihydropyridine calcium channel antagonists, β-adrenoceptor antagonists (β-blockers), and amiodarone are the pharmacologic agents most commonly used to achieve rate control. In patients with drug-resistant AF, atrioventricular nodal ablation (or modification) with implantation of a permanent pacemaker is an alternative therapy. Conversion to sinus rhythm can best be achieved by electrical cardioversion. In selected patients, pharmacologic cardioversion can also be attempted. The use of antiarrhythmic drugs for the maintenance of sinus rhythm depends on several factors: (i) the nature of the arrhythmia (first attack, paroxysmal AF with frequent attacks, paroxysmal AF with infrequent attacks, or persistent AF); (ii) the associated symptoms; and (iii) the risk of severe adverse effects associated with the chosen drug. If the administration of an antiarrhythmic drug is appropriate, the choice of the drug must be tailored to the specific characteristics of the given patient. In lone AF, class Ic antiarrhythmic drugs are the best tolerated. These agents should be combined with a calcium channel antagonist or a β-blocker to prevent rapid ventricular response in the case of conversion of AF to atrial flutter. In this situation, catheter ablation of atrial flutter at the isthmus (hybrid therapy) should be performed. All class I antiarrhythmic agents should be avoided in patients with structural heart disease. Alternative approaches that may be used if sinus rhythm cannot be maintained with drug therapy include: (i) the ablation of arrhyth-mogenic pulmonary veins; (ii) the implantation of an atrial defibrillator; (iii) the use of specific pacing sites; or (iv) pacing modes. Whether these approaches will reach clinical relevance merits further investigation. Intraoperative catheter ablation or surgical ablation (maze procedure) seems a promising approach for curing AF in patients undergoing cardiac surgery. Among all of the available treatment options, the most consistent proof of efficacy in reducing mortality and morbidity from AF exists for antithrombotic treatment.     

Atrial fibrillation. The therapeutic options

Atrial fibrillation (AF) is a common cardiac arrhythmia which is particularly prevalent among the elderly. In patients with AF of recent onset, restoration of sinus rhythm may be feasible and this can be achieved by DC cardioversion, or by the use of one of a number of drugs including amiodarone, flecainide or propafenone. Neither digoxin nor the calcium antagonists facilitate the restoration of sinus rhythm. Recurrence of AF is common after successful cardioversion and, although long term antiarrhythmic drug therapy may help to maintain sinus rhythm, all such drugs are potentially toxic and can have important proarrhythmic actions. In patients with chronic AF, restoration of sinus rhythm is rarely possible and treatment is directed towards control of the ventricular response rate, which may be achieved with digoxin and/or a rate-limiting calcium antagonist such as verapamil or diltiazem; beta-blockers may also be used although they appear to impair effort tolerance. In addition, long term anticoagulation may be indicated to reduce the risks of systemic embolisation, even in patients with 'nonrheumatic' AF; antiplatelet drugs are of no apparent value in this context. A minority of patients present with AF associated with ventricular pre-excitation; in these individuals both digoxin and the calcium antagonists are contraindicated and the ventricular response rate should be controlled with flecainide, amiodarone or propafenone.     

Pharmacological cardioversion of atrial fibrillation: current management and treatment options

Atrial fibrillation (AF) is the most common form of arrhythmia, carrying high social costs. It is usually first seen by general practitioners or in emergency departments. Despite the availability of consensus guidelines, considerable variations exist in treatment practice, especially outside specialised cardiological settings. Cardioversion to sinus rhythm aims to: (i) restore the atrial contribution to ventricular filling/output; (ii) regularise ventricular rate; and (iii) interrupt atrial remodelling. Cardioversion always requires careful assessment of potential proarrhythmic and thromboembolic risks, and this translates into the need to personalise treatment decisions. Among the many clinical variables that affect strategy selection, time from onset is crucial. In selected patients, pharmacological cardioversion of recent-onset AF can be a safely used, feasible and effective approach, even in internal medicine and emergency departments. In most cases of recent-onset AF, pharmacological cardioversion provides an important--and probably more cost effective--alternative to electrical cardioversion, which can then be employed as a second-line therapy for nonresponders. Class IC agents (flecainide or propafenone), which can be safely used in hospitalised patients with recent-onset AF without left ventricular dysfunction, can provide rapid conversion to sinus rhythm after either intravenous administration or oral loading. Although intravenous amiodarone requires longer conversion times, it is still the standard treatment for patients with heart failure. Ibutilide also provides good conversion rates and could be used for AF patients with left ventricular dysfunction (were it not for high costs). For long-lasting AF most pharmacological treatments have only limited efficacy and electrical cardioversion remains the gold standard in this setting. However, a widely used strategy involves pretreatment with amiodarone in the weeks before planned electrical cardioversion: this provides optimal prophylaxis and can sometimes even restore sinus rhythm. Dofetilide may also be capable of restoring sinus rhythm in up to 25-30% of patients and can be used in patients with heart failure. The potential risk of proarrhythmia increases the need for careful therapeutic decision making and management of pharmacological cardioversion. The results of recent trials (AFFIRM [Atrial Fibrillation Follow-up Investigation of Rhythm Management] and RACE [Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation]) on rate versus rhythm control strategies in the long term have led to a generalised shift in interest towards rate control. Although carefully designed studies are required to better define the role of pharmacological rhythm control in specific AF settings, this alternative option remains a recommendable strategy for many patients, especially those in acute care.     

Antiarrhythmic drugs in atrial fibrillation: an overview of new agents,their mechanisms of action and potential clinical utility

Despite recent advances in our understanding of the mechanism of atrial fibrillation (AF), effective treatment remains difficult in many patients. Pharmacotherapy remains the mainstay of treatment and includes control of ventricular rate as well as restoration and maintenance of sinus rhythm. The currently available antiarrhythmic drugs are particularly effective in converting paroxysmal AF to sinus rhythm and in enhancing the positive effect of electrical cardioversion, but are limited in their efficacy in maintaining sinus rhythm. Moreover, there are limited options in the setting of co-existing ischaemic heart disease, left ventricular dysfunction and structural heart diseases. New drugs added to our clinical armamentarium have been, or are being, developed to combine better efficacy and lack of pro-arrhythmic effects. These developments have gained more interest particularly with the recent debate over rate control versus rhythm control for AF. Although some of these agents are promising, their uptake in clinical practice will not only depend on their efficacy as antiarrhythmic agents but also on their safety in acutely terminating AF and in long-term maintenance of sinus rhythm or rate control in the community.     

Antiarrhythmic drugs in atrial fibrillation: an overview of new agents, their mechanisms of action and potential clinical utility

Despite recent advances in our understanding of the mechanism of atrial fibrillation (AF), effective treatment remains difficult in many patients. Pharmacotherapy remains the mainstay of treatment and includes control of ventricular rate as well as restoration and maintenance of sinus rhythm. The currently available antiarrhythmic drugs are particularly effective in converting paroxysmal AF to sinus rhythm and in enhancing the positive effect of electrical cardioversion, but are limited in their efficacy in maintaining sinus rhythm. Moreover, there are limited options in the setting of co-existing ischaemic heart disease, left ventricular dysfunction and structural heart diseases. New drugs added to our clinical armamentarium have been, or are being, developed to combine better efficacy and lack of pro-arrhythmic effects. These developments have gained more interest particularly with the recent debate over rate control versus rhythm control for AF. Although some of these agents are promising, their uptake in clinical practice will not only depend on their efficacy as antiarrhythmic agents but also on their safety in acutely terminating AF and in long-term maintenance of sinus rhythm or rate control in the community.     

Atrial fibrillation in the elderly: facts and management

Although atrial fibrillation is not widely known by the general public, in developed countries it is the most common arrhythmia. The incidence increases markedly with advancing age. Thus, with the growing proportion of elderly individuals, atrial fibrillation will come to represent a significant medical and socioeconomic problem. The consequences of atrial fibrillation have the greatest impact. The risk of thromboembolism is well known; other outcomes of atrial fibrillation are less well recognised, such as its relationship with dementia, depression and death. Such consequences are responsible for diminished quality of life and considerable economic cost. Atrial fibrillation is characterised by rapid and disorganised atrial activity, with a frequency between 300 and 600 beats/minute. The ventricles react irregularly, and may contract rapidly or slowly depending on the health of the conduction system. Clinical symptoms are varied, including palpitations, syncope, dizziness or embolic events. Atrial fibrillation may be paroxysmal, persistent or chronic, and a number of attacks are asymptomatic. Suspicion or confirmation of atrial fibrillation necessitates investigation and, as far as possible, appropriate treatment of underlying causes such as hypertension, diabetes mellitus, hypoxia, hyperthyroidism and congestive heart failure. In the evaluation of atrial fibrillation, cardiac exploration is invaluable, including electrocardiogram (ECG) and echocardiography, with the aim of detecting cardiac abnormalities and directing management. In elderly patients (arbitrarily defined as aged >75 years), the management of atrial fibrillation varies; it requires an individual approach, which largely depends on comorbid conditions, underlying cardiac disease, and patient and physician preferences. This management is essentially based on pharmacological treatment, but there are also nonpharmacological options. Two alternatives are possible: restoration and maintenance of sinus rhythm, or control of ventricular rate, leaving the atria in arrhythmia. Pharmacological options include antiarrhythmic drugs, such as class III agents, beta-blockers and class IC agents. These drugs have some adverse effects, and careful monitoring is necessary. The nonpharmacological approach to atrial fibrillation includes external or internal direct-current cardioversion and new methods, such as catheter ablation of specific foci, an evolving science that has been shown to be successful in a very select group of atrial fibrillation patients. Another serious challenge in the management of chronic atrial fibrillation in older individuals is the prevention of stroke, its primary outcome, by choosing an appropriate antithrombotic treatment (aspirin or warfarin). Several risk-stratification schemes have been validated and may be helpful to determine the best antithrombotic choice in individual patients.     

Use of β-Blockers in Atrial Fibrillation

Atrial fibrillation is the most common arrhythmia in the general population and is frequently associated with organic heart disease. β-adrenoceptor antagonists (β-blockers) are very effective in preventing atrial fibrillation after coronary artery bypass surgery It has been shown recently that the β-blocker metoprolol controlled release/extended release (CR/XL) is also effective in maintaining sinus rhythm after conversion of atrial fibrillation. There is concern that class I antiarrhythmic drugs, such as quinidine, disopyramide, and flecainide in particular, may increase mortality. The risk of proarrhythmia associated with β-blocker treatment is very low. Therefore β—blockers, such as metoprolol CR/XL, may be the first line of treatment to maintain sinus rhythm, especially after myocardial infarction and in patients with chronic heart failure and in those with arterial hypertension. In patients with persistent atrial fibrillation, AV-nodal conduction-slowing drugs, such as calcium channel antagnoists and β-blockers are used to control the ventricular rate during atrial fibrillation. Several studies clearly show that β-blockers alone, or in combination with digoxin are very effective in controlling the ventricular rate at rest and during exercise, β-blockers are effective in maintaining sinus rhythm and controlling the ventricular rate during atrial fibrillation. Given these effects and their favorable effects on mortality, β-blockers should be considered as first-line agents in the management of patients with atrial fibrillation.     

Angiotensin II receptor blockers in the prevention of atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia. While antiarrhythmic agents and electrical cardioversion are highly effective in restoring sinus rhythm, the results obtained in prevention of recurrences are disappointing. Recently, angiotensin II has been recognized as a key factor in atrial structural and electrical remodeling associated with AF. So there are several potential mechanisms by which inhibition of the renin-angiotensin-aldosterone system may reduce AF. In this review, we report the results of studies evaluating the effect of angiotensin II receptor blockers (ARBs) in various clinical settings (i.e., lone AF, hypertension, high-risk patients, congestive heart failure, secondary prevention). However, many of these studies are small and retrospective and have a limited follow-up; moreover, since AF is related to several causes, chiefly heart diseases, patients with different characteristics have often been enrolled. Thus, it is not surprising that the results obtained are frequently conflicting. With these limitations and considering only the results of larger studies with longer follow-up, ARBs are effective in preventing AF in patients with congestive heart failure or hypertension with left ventricular hypertrophy or coronary artery/cerebrovascular disease. In any case, the use of ARBs is not recommended at present in clinical practice to prevent AF.     

Is Oral Sotalol Effective in Converting Atrial Fibrillation to Sinus Rhythm?

d,l-Sotalol is a noncardioselective β-blocker that has class III antiarrhythmic activity. It is often used to convert atrial fibrillation (AF) to normal sinus rhythm. Since class III agents increase action potential duration and refractoriness in atrial tissue without affecting conduction, they are theoretically considered ideal agents for the treatment of reentrant arrhythmias such as AF. We reviewed the literature evaluating the efficacy of Sotalol for restoring sinus rhythm in patients with acute or chronic AF. Articles indexed on MEDLINE (1966–1996) and referenced articles not identified by MEDLINE that compared Sotalol with placebo or another antiarrhythmic agent were included. Sotalol was significantly inferior to quinidine in converting AF of recent onset (< 48 hrs) to sinus rhythm. In patients with duration of AF of more than 48 hours, Sotalol was significantly less effective than quinidine and comparable with placebo. Conversion rates for Sotalol in all studies combined ranged from 8–49%. Published studies do not support the drug for conversion of AF to sinus rhythm. Larger well-designed studies are required to evaluate its efficacy and optimum dosage for this indication. Until further data are available, pharmacologic cardioversion with traditional class I antiarrhythmic agents may be preferable as they are effective particularly for recent-onset AF.     

Dofetilide: a review of its use in atrial fibrillation and atrial flutter

Dofetilide is a 'pure' class III antiarrhythmic agent which has demonstrated efficacy in the conversion of atrial fibrillation or flutter to sinus rhythm and the maintenance of sinus rhythm. By blocking the rapid component of the cardiac delayed rectifier potassium current (I(Kr)), dofetilide prolongs the cardiac action potential duration and the effective refractory period. This is thought to increase the likelihood of a re-entrant wavefront encountering refractory tissue and terminating the arrhythmia. Preliminary findings from the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) and SAFIRE-D (Symptomatic Atrial Fibrillation Investigation and Randomized Evaluation of Dofetilide) studies suggest that oral dofetilide is effective in the conversion of atrial fibrillation or flutter to sinus rhythm. Both studies have yet to be published in full. In SAFIRE-D, dofetilide 500microg twice daily for 3 days achieved a conversion rate of 32% compared with a 1% rate for placebo. A similar conversion rate was achieved after 3 days in EMERALD with dofetilide 500microg twice daily (29%) which was significantly greater than that achieved with sotalol 80mg twice daily (6%; p < 0.05). Oral dofetilide also appears to be effective in the maintenance of sinus rhythm. An abstract report of EMERALD participants who had been converted to sinus rhythm showed that 71% of patients who received oral dofetilide remained in sinus rhythm after 6 months (compared with 26% of placebo and 59% of sotalol recipients: both p < 0.05). Restoration of sinus rhythm using intravenous dofetilide is more likely in patients with recent-onset versus prolonged-duration arrhythmia, and in those with atrial flutter rather than atrial fibrillation. Limitations of comparative data for intravenous dofetilide are such that few conclusions can be drawn. Although generally well tolerated in clinical trials, dofetilide has proarrhythmic potential. Torsade de pointes ventricular tachycardia was reported in up to 3.3% of patients who received oral dofetilide in the DIAMOND (Diamond Investigations of Arrhythmia and Mortality on Dofetilide) studies, although only a small proportion of patients in these studies had atrial fibrillation; most episodes occurred within the first 3 days. Whether the propensity of dofetilide for this life-threatening arrhythmia is similar to that of other class III antiarrhythmic agents has yet to be determined. Importantly, the long term use of oral dofetilide in patients at high risk for sudden cardiac death is not associated with an increased risk of mortality, although these DIAMOND findings cannot necessarily be extrapolated to patients with atrial fibrillation. CONCLUSIONS: Dofetilide offers an alternative to currently available antiarrhythmic agents for the pharmacological conversion of atrial fibrillation or atrial flutter to sinus rhythm and for the maintenance of sinus rhythm after cardioversion. However, further comparative data are necessary before its definitive place can be determined.     

Rate control versus rhythm control for the management of atrial fibrillation: the verdict of the AFFIRM trial

Atrial fibrillation is the most common sustained cardiac arrhythmia encountered in clinical practice that affects cardiovascular morbidity and mortality and generates significant healthcare costs. There are two approaches for the management of atrial fibrillation: rate control and rhythm control. Rate-control strategy involves using rate-controlling agents such as beta-blockers, calcium channel blockers or digoxin, or a combination thereof to control symptoms while allowing atrial fibrillation to persist. Rhythm-control strategy involves cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm. Although each strategy has its own advantages as well as limitations, it has long been debated which of the strategies offers better long-term outcomes and thus should be the preferred and recommended approach for the management of patients with atrial fibrillation. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study was the first large-scale randomised study to address this important issue. In this article, the long awaited verdict of the AFFIRM study with its implications for the clinical management of patients with atrial fibrillation is discussed.     

Drug-induced atrial fibrillation

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and an important cause of hospitalization, morbidity, and mortality. A myriad of drugs can induce AF. However, drug-induced AF (DIAF) receives little attention. Thus, this review is an attempt to attract the attention on this adverse effect. AREAS COVERED: Published reports of drug-induced AF (DIAF) are reviewed in this paper, from January 1974 to December 2011, using the PubMed/Medline database and lateral references. EXPERT OPINION: In most cases, DIAF is paroxysmal and terminates spontaneously, but sometimes AF persists and it is necessary to perform a cardioversion to restore sinus rhythm and avoid progression to persistent AF. Because of the short duration of DIAF, in addition to physicians/patients not being knowledgeable about this side effect, the real incidence and clinical consequences of DIAF are presently unknown. DIAF is an increasing problem, as some widely prescribed drugs can present this adverse effect. The risk is expected to increase in the elderly and in patients with comorbidities. It is important that physicians understand the significance of DIAF, to increase the collaboration between cardiac and non-cardiac professionals, and to educate patients to make them aware of this adverse side effect.     

The drug treatment of atrial fibrillation.

1. Atrial fibrillation is an inefficient cardiac rhythm associated with impaired exercise tolerance, exertional dyspnoea, palpitation and a substantial risk of thromboembolism. 2. The first decision in management is to consider cardioversion which can be achieved in suitable cases electrically, or pharmacologically with a class Ic antiarrhythmic drug like flecainide or propafenone. 3. Prophylaxis in paroxysmal atrial fibrillation is best achieved with a class Ic drug or a class III drug such as sotalol or amiodarone. 4. Control of ventricular rate in chronic atrial fibrillation can be achieved by pharmacological manipulation of the atrioventricular node by digoxin alone, or in combination with the calcium channel blockers verapamil or diltiazem, or beta-adrenoceptor blockers with intrinsic sympathomimetic activity like pindolol or xamoterol. 5. In view of the considerable risk of thromboembolism in patients with chronic atrial fibrillation anticoagulation or at least treatment with aspirin should be considered.     

Dronedarone

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with substantial morbidity and mortality. Dronedarone is an amiodarone-like benzofuran which lacks the iodine moiety and presents a methane sulfonyl group that decreases its lipophilicity, thus shortening the half-life and decreasing tissue accumulation. Like amiodarone, dronedarone blocks multiple cardiac ion channels and β-adrenoceptors, presenting electrophysiological characteristics of all four Vaughan Williams classes of antiarrhythmic drugs. In clinical trials, dronedarone has been found effective for both rhythm and rate control. Dronedarone was more effective than placebo in maintaining sinus rhythm in patients with paroxysmal and/or persistent AF and was also effective for ventricular rate control during AF recurrences, providing incremental rate control on top of standard drugs in permanent AF. Furthermore, in the ATHENA trial, dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with nonpermanent AF. Even when dronedarone was less effective than amiodarone in decreasing AF recurrence, it had a better safety profile, being devoid of thyroid, pulmonary and neurological toxicity. This review analyzes the electrophysiological and pharmacological properties, as well as the efficacy and safety of dronedarone in patients with atrial fibrillation.     

心房颤动药物复律治疗进展

心房颤动是一种常见的心律失常。药物复律是最常用的复律方法。应根据心房颤动类型、心房颤动持续时间、引起心房颤动的基础疾病、左心功能等选择正确的治疗策略和合适的复律药物。     

窦性冲动疏导术治疗心房颤动的长期随访研究

目的 观察窦性冲动疏导术治疗心房颤动的长期疗效.方法 1996年5月至2002年6月,9例患者接受了窦性冲动疏导术,消除多子波折返激动.其中7例同时进行二尖瓣置换.术后对9例患者进行不定期随访,随访过程中,患者接受心电图,彩色超声心动图检测.结果 2例于随访l后及1.5年后失访,其他7例患者随访7 ～13年.术后1年内心功能Ⅰ级5例,Ⅱ级4例；窦性心律2例,类窦性心律7例；Ⅲ度AV-B并发症1例,心肌病进展1例,肾功能不全1例；心房A/E峰为0.3者2例,0.4者4例,0.5者2例,0.6者1例.有6例于术后1～2周内先后出现过早搏、阵发性室上性心动过速等心律失常,未服用抗心律失常药自行恢复规律的心律.结论 窦性冲动疏导术是一种可以有效消除心房多子波折返激动的术式,消除了多子波折返激动就可以消除心房颤动.但是得到的却是一种永久性的室上心律.如果对这种单一的室上心律起搏点进行消融,失去了异位起搏点后可以得到的应该是窦性心律.     

Apelin plasma levels predict arrhythmia recurrence in patients with persistent atrial fibrillation

Low levels of the regulatory peptide apelin have been reported in patients with lone atrial fibrillation (AF). We evaluate the potential utility of assessing apelin plasma levels as a predictor of AF recurrence in individuals presenting for electrical cardioversion. Plasma levels of apelin, brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein were measured in 93 patients, with persistent AF before successful external electrical cardioversion. Significantly lower apelin plasma levels were found in patients with AF recurrence as respect to population with persistence of sinus rhythm during a six months follow-up. The hazard increased with duration of AF, left atrial dimension, BNP concentrations. Subjects with apelin levels below the median had a hazard ratio of 3.1 of arrhythmia recurrence with respect to those with high apelin levels (p<0.05). A significant difference in BNP levels was found between patients with and without AF recurrence during the follow-up. After adjusting for potential confounders, both BNP and apelin retained their statistical significance as independent predictors of arrhythmia recurrence. Patients with both low apelin and elevated BNP had a worse prognosis compared with those with either low apelin or elevated BNP alone. Low plasma apelin levels before external electrical cardioversion are an independent prognostic factor for arrhythmia recurrence in patients with AF treated with antiarrhythmic drugs. Apelin may be of particular value for the identification of high-risk patients in addition to BNP.     

胺碘酮治疗冠心病心房颤动撤药时机的相关性研究

目的研究胺碘酮联合氯沙坦治疗阵发性心房颤动,心律转为窦性后逐渐加用β受体阻滞剂倍他乐克后胺碘酮撤药时机的相关性因素分析。方法胺碘酮联合氯沙坦治疗,6个月后已复律患者30例,给予从小剂量开始逐渐加量,维持心室率在55～65次/min,减少胺碘酮用量,在3个月内撤掉胺碘酮,从撤药开始随访半年,观察患者窦性心律的维持情况,分析影响撤药成功的因素。结果胺碘酮联合氯沙坦治疗可使患者心功能改善(P<0.05),左房内径左心室舒张末内径缩小、EF值增大(P<0.01)。倍他乐克逐渐替换胺碘酮后房颤复发9例(30%),维持21例(70%),差异有统计学意义(P<0.01)。用Logistic回归统计方法,分析患者窦性心律的维持与撤药前左房内径相关(P<0.01,OR1.30,95%CI1.01～1.74)),左房<40mm的患者不易复发房颤。结论氯沙坦治疗在应用基础上倍他乐克替换胺碘酮在临床有其可行性,且撤药成功与撤药前患者左心房内经相关,远期疗效及对心血管事件的影响有待进一步观察。