Antiarrhythmic Drug Therapy in the Management of Atrial Fibrillation

Antiarrhythmic Drugs for AF. Antiarrhythmic drugs have been used for the acute conversion of atrial fibrillation to sinus rhythm, as well as for the long-term maintenance of sinus rhythm. In recent years, concerns regarding antiarrhythmic drug efficacy as well as safety have prompted a re-examination of the indications for antiarrhythmic therapy in patients with atrial fibrillation. This review will focus on the safety and efficacy of antiarrhythmic therapy in the acute and chronic management of patients with atrial fibrillation.     

Assessment of Rhythm and Rate Control in Patients with Atrial Fibrillation

A recent series of randomized prospective clinical trials that compared rate control with rhythm control in patients with atrial fibrillation (AF) found no significant difference in primary outcome between the two strategies. However, these trials lacked clear criteria for defining "successful" rate or rhythm control. Various measures have been used to gauge the success of antiarrhythmic drug therapy, including time to first recurrence of AF, any AF recurrence, AF burden, and a reduction in symptoms. Determining the success of antiarrhythmic therapy can be relatively straightforward by using how patients feel during therapy as a key endpoint. Most patients are satisfied with a major reduction in symptomatic AF episodes and can live comfortably with occasional episodes of AF. For those who are bothered by even infrequent, brief AF episodes, a treatment regimen that eliminates nearly all AF recurrences is required, although often hard to achieve. Catheter ablation may be necessary to achieve a successful outcome in these patients. Suppression of AF in a patient at high risk of stroke does not, however, remove the need for concomitant warfarin therapy. The endpoints of ventricular rate control are not clear, and the recently published rhythm versus rate control trials lacked standard criteria for judging acceptable rate control. One relatively simple method is to try and achieve a 24-hour heart rate that mimics expected normal sinus rhythm. It is important to achieve good rate control to minimize symptoms and the risk of tachycardia-mediated cardiomyopathy.     

Higher Rate of Recurrent Atrial Flutter and Atrial Fibrillation Following Atrial Flutter Ablation After Cardiac Surgery

Atrial Flutter After Cardiac Surgery . Introduction: Atrial flutter (AFL) is common after cardiac surgery. However, the types of post‐cardiac surgery AFL, its response to catheter‐based radiofrequency ablation, and its relationship to atrial fibrillation (AF) are unknown. Methods and Results: We retrospectively studied all patients who underwent mapping and ablation for AFL after cardiac surgery from January 1990 to July 2004. One hundred randomly selected patients without prior cardiac surgery (PCS) who underwent mapping and ablation of AFL served as the control population. A total of 236 patients formed the study population (mean age 62 + 13 years, 22% female) and 100 patients formed the control population (mean age 60 + 13 years, 25% female). The majority of patients without PCS had cavo‐tricuspid isthmus (CTI)‐dependent AFL when compared to patients with PCS (93% vs 72%, respectively, P < 0.0001). In contrast, scar‐related AFL was more common in patients with PCS as compared to patients without PCS (22% vs 3%, P < 0.0001). Predictors of scar related AFL in multivariable regression analysis included PCS and left‐sided AFL. Acute success rates and complications were similar between the groups. When compared to patients with AFL ablation without PCS, those that had AFL after PCS had higher rates of recurrence of both AFL (1% vs 12%, P < 0.0001; mean time to recurrence 1.85 years) and AF (16% vs 28%, P = 0.02; mean time to recurrence 2.67 years). Conclusion: Despite ablation of AFL, patients with PCS have a higher rate of AFL and AF when compared to patients without PCS who underwent ablation of atrial flutter during long‐term follow‐up. (J Cardiovasc Electrophysiol, Vol. pp. 760‐765, July 2010)     

A Review of Clinical Trials Assessing the Efficacy and Safety of Newer Antiarrhythmic Drugs in Atrial Fibrillation

Clinical trials assessing the efficacy of anti- arrhythmic drugs for terminating atrial fibrillation have demonstrated that rate control drugs have little to no added efficacy compared to placebo; however, spontaneous conversion of recent-onset atrial fibrillation is common. Antiarrhythmic drugs such as oral dofetilide, oral bolus-flecainide and propafenone and intravenous ibutilide all have a role in terminating atrial fibrillation. Active comparator trials have demonstrated that amiodarone is more efficacious in maintaining sinus rhythm than propafenone and sotalol. Multiple trials have demonstrated the safety of amiodarone, sotalol, dofetilide and azimilide in a post-myocardial infarction population and amiodarone and dofetilide in a congestive heart failure population. Newer antiarrhythmic agents, some with novel mechanisms of action, will add to the pharmacologic armamentarium in treating atrial fibrillation.     

The Future of Atrial Fibrillation Therapy

Today management of atrial fibrillation (AF) centers on restoration and maintenance of normal sinus rhythm or control of the ventricular rate response to AF. Current guidelines state that rhythm and rate control strategies should be considered therapeutically equivalent, but recognize that no "one size fits all," an approach consistent with growing recognition of the heterogeneity of AF. As data from the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial clearly demonstrate, conventional antiarrhythmics have a role in highly symptomatic AF accompanied by decreased quality of life. However, for many AF patients such drugs lack efficacy, have potentially serious side effects, and are poorly tolerated. In parallel with the development of more effective and safer antiarrhythmics, nontraditional approaches to prevention and treatment of AF are being explored. Treatments not considered "antiarrhythmic" that may prevent or forestall AF include aggressive antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and some, but not all, beta-blockers and calcium channel antagonists, especially when used as adjunctive therapy. Other approaches include statins, steroids, and fish oil to reduce atrial fibrosis and inflammation, and pacemakers to prevent bradycardia-mediated AF and as a pacing preventive strategy in selected patients. Ablative techniques with potential to cure AF are gaining popularity, but are not yet simple, straightforward, and risk-free procedures. In the future, treatment of AF will progress beyond today's focus on AF as a purely electrocardiographic disease toward a patient and context-specific management strategy involving multiple treatment modalities.     

A Prospective Study of Atrial Fibrillation After Cardiac Surgery

Background: Atrial fibrillation (AF) is a commonly encountered arrhythmia following cardiac surgery and when sustained, may be associated with significant morbidity. Methods: This large prospective investigation examined a variety of clinical and P wave signal-averaged electrocardiogram (SAECG) parameters to identify independent predictors of AF following cardiac surgery. A total of 272 patients underwent P wave SAECG recording and analysis prior to surgery. Information on their clinical, surgical, and hemodynamic characteristics as well as hospital course was collected. Patients were followed during their postoperative course with telemetry and ECGs. Results: During an observation period of up to 14 days, 79 patients (29%) developed AF 2.5 ± 1.9 days after surgery. Patients who developed AF following cardiac surgery were more likely to be older, undergo valve surgery, to have ejection fraction (EF) < 40%, to have P wave duration on SAECG >140 ms (all P < 0.01), and to take digoxin preoperatively (P < 0.05). A multivariate analysis found that only P wave duration on SAECG >140 ms and EF < 40% were independent predictors of AF following cardiac surgery. The odds ratio of P wave duration on SAECG >140 ms and EF < 40% for the development of AF following cardiac surgery was 3.1 and 2.8, respectively, and 8.7 when combined. Conclusions: Thus, the presence of preexisting abnormal atrial substrate as detected by P wave prolongation on SAECG, and implicated by EF < 40%, clearly predicted a higher risk of AF following cardiac surgery and may provide clinicians with an effective means of identifying those at greatest risk.     

心房颤动的药物治疗进展

心房颤动是临床上最常见的心律失常类型,患病率随年龄增长而增加,药物是心房颤动治疗的首选,由于传统抗心律失常药物潜在的致心律失常作用及心脏外的不良反应,故而在心房颤动的治疗中受限。近年一些新药的研制给心房颤动的治疗带来了新的希望,也为临床医生提供了更多的选择。现就心房颤动药物治疗进展做一综述。     

Conversion of Atrial Fibrillation by the Experimental Antiarrhythmic Drug Tedisamil in Two Canine Models

INTRODUCTION: Tedisamil is an experimental bradycardic agent possessing action potential-prolonging effects. It has been proven effective in terminating ventricular arrhythmias in several animal models and atrial flutter in a conscious dog model. There are no reports to date evaluating tedisamil's efficacy in terminating atrial fibrillation (AF). METHODS AND RESULTS: Two different canine models of AF were used. One group of dogs (n = 6) was subjected to 28 days of chronic fibrillatory pacing at 50 Hz using an implantable neural stimulator. Sustained AF was achieved in all dogs within 14 days of initiating pacing. A second set of dogs (n = 5) had AF induced via bilateral vagal stimulation. Tedisamil 1 mg/kg was 100% effective in terminating AF in both models. Cardioversion was associated with a statistically significant prolongation of the fibrillatory cycle length immediately before return to normal sinus rhythm in both models. A dose-response trial was performed in the vagal AF group as well as in a second group of three dogs that underwent chronic fibrillatory pacing. The efficacy of tedisamil was dose dependent, with limited efficacy at 0.1 and 0.3 mg/kg intravenously in both models. Tedisamil was able to prevent reinduction of sustained AF 30 minutes after administration of 1 mg/kg in the chronic pacing model in all dogs. Side effects included minor hypersalivation in most dogs receiving the 1 mg/kg dose. No ventricular ectopy or arrhythmias were observed. CONCLUSION: Tedisamil is effective for conversion of sustained AF to normal sinus rhythm in two different models of AF.     

Pharmacological Approach for the Prevention of Atrial Fibrillation After Cardiovascular Surgery

Atrial fibrillation (AF) is a common complication of cardiovascular surgery. The two most important risk factors for its development are advancing age and a preoperative history of AF. Long-term sequelae, such as a stroke, are uncommon, however, atrial fibrillation frequently results in increased length and cost of hospitalization. Strategies to prevent postoperative AF include perioperative beta-blockers, amiodarone, and atrial pacing. These strategies are most effective in high-risk patients. When AF does occur, treatment includes control of the ventricular rate, systemic anticoagulation, and conversion to sinus rhythm.     

Persistent Atrial Flutter in Patients Treated for Atrial Fibrillation with Amiodarone and Propafenone:

INTRODUCTION: Antiarrhythmic drugs have been reported to promote the conversion of atrial fibrillation to atrial flutter in patients with paroxysmal atrial fibrillation. However, information about the electrophysiologic mechanism and response to radiofrequency ablation of these drug-induced atrial flutters is limited. Furthermore, the determinants of the development of persistent atrial flutter in patients treated for atrial fibrillation with antiarrhythmic drugs are still unknown. METHODS AND RESULTS: Among the 136 patients treated for atrial fibrillation with amiodarone (n = 96) or propafenone (n = 40), 15 (11%, mean age 65.5 +/- 12.3 years) were identified to have subsequent development of persistent atrial flutter based on surface ECG characteristics during antiarrhythmic drug treatment. The mean interval between the beginning of drug treatment and the onset of atrial flutter was 5.0 +/- 5.5 months. Intracardiac mapping and entrainment studies revealed that 11 patients had counterclockwise typical atrial flutter, and 4 had clockwise typical atrial flutter. All 15 patients underwent successful ablation with creation of complete bidirectional isthmus conduction block. After a mean follow-up of 12.3 +/- 4.2 months, 14 (93%) of 15 patients who underwent successful ablation and continued taking antiarrhythmic drugs have remained in sinus rhythm. Univariate analysis of clinical variables demonstrated that only atrial enlargement was significantly related to the occurrence of persistent atrial flutter. CONCLUSION: In patients with atrial fibrillation, persistent typical atrial flutter might occur during antiarrhythmic drug treatment, and atrial enlargement was a risk factor for the development of such an arrhythmia. Radiofrequency ablation and continuation of pharmacologic therapy offered a safe and effective means of achieving and maintaining sinus rhythm.     

心房颤动导管消融后复发和抗心律失常药物的应用

心房颤动导管消融术后复发是一个需要进一步认识和解决的临床难题,包括抗心律失常药物在内的联合治疗是现阶段减少复发的可行方案。     

心房颤动的抗心律失常治疗选择

心房颤动抗心律失常治疗尤为重要。胺碘酮类似物、选择性心房离子通道阻滞剂、缝隙连接调节剂、非抗心律失常药物的联合应用给心房颤动的药物治疗带来了新的希望。射频消融不断发展,但仍存在一些问题有待解决。外科Cox-maze-Ⅳ消融术也在不断发展。现就心房颤动抗心律失常的治疗选择作一综述。     

Analysis of the Surface Electrocardiogram for Monitoring and Predicting Antiarrhythmic Drug Effects in Atrial Fibrillation

Specific antiarrhythmic therapy with class I and III drugs for atrial fibrillation (AF) conversion and prevention of its recurrence is frequently utilized in clinical practice. Besides being only moderate effective, the utilization of antiarrhythmic drugs may be associated with serious side effects. In the clinical setting it is difficult to directly evaluate the effects of antiarrhythmic drugs on the individual patient’s atrial electrophysiology, thereby predicting their efficacy in restoring and maintaining sinus rhythm. Analysis of the surface electrocardiogram in terms of P-wave signal averaged ECG during sinus rhythm and spectral characterization of fibrillatory waves during AF for evaluation of atrial antiarrhythmic drug effects is a new field of investigation. Both techniques provide reproducible parameters for characterizing atrial electrical abnormalities and seem to contain prognostic information regarding antiarrhythmic drug efficacy. Further research is needed which elucidates the most challenging clinical questions in AF management whom to place on antiarrhythmic drug treatment and what antiarrhythmic drug to prescribe. Analysis of the surface ECG might have the potential to answer these questions.     

Mechanisms of Termination of Atrial Fibrillation by Class I Antiarrhythmic Drugs:

Sodium channel blocking drugs (Class I antiarrhythmic agents) have been used for the termination of atrial fibrillation (AF) and for sinus rhythm maintenance for almost 100 years. Despite this long history, the mechanisms that underlie their efficacy in AF remain poorly understood. Classic notions about the determinants of cardiac reentry, as embodied in leading circle theory, and of AF, as reflected in the multiple wavelet hypothesis, suggest that cardiac conduction slowing should promote, rather than prevent, AF. This article reviews the evidence (both clinical and experimental) for the efficacy and mechanisms of action of Class I antiarrhythmic agents in AF. Application of mathematical models of AF to the evaluation of Class I mechanisms is discussed, and recent insights into the latter are presented. A better understanding of the ways in which Na⁺ channel blockers affect AF will be useful, not only for new antiarrhythmic drug development but also for gaining insight into the mechanisms of the arrhythmia. (J Cardiovasc Electrophysiol, Vol. 14, pp. S133-S139, October 2003, Suppl.)     

Atrial Fibrillation After Cardiac Surgery: Update on the Evidence on the Available Prophylactic Interventions

Post-operative atrial fibrillation is very common. It is associated with increased length of ICU and hospital stay, and costs of post-operative care of patients after cardiac surgery. More then seventy trials on the pharmacological and non-pharmacological interventions were conducted since 1970's. Meta-analysis of these trials, together with detailed analysis of the largest of these trials suggested that conventional beta-blockers, sotalol, amiodarone and bi-atrial overdrive pacing are effective in prevention of post-operative atrial fibrillation. Amiodarone and bi-atrial pacing may decrease the length of hospital stay.