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.     

Proarrhythmic effects of antiarrhythmic drugs]

The proarrhythmic effects of antiarrhythmic drugs are complications which have been described over several decades but the mechanisms (reentry, increased automaticity, ectopic faci, induced repetitive activity, vagal or adrenergic triggers) and the predisposing factors (underlying cardiac disease, previous severe arrhythmia, metabolic disorders, ischaemia, etc...) have only recently been identified. The appreciation of their true frequency poses problems of methodology (mode of recruitment, therapeutic converse proof), of definitions and depends to a great extent on the methods of detection used. Their severity cannot be denied and has been demonstrated both in experience of isolated cases and in recent prospective studies, the conclusions of which must be interpreted critically. Proarrhythmic effects may be observed at atrial (vagal or sympathetic arrhythmias, 1/1 flutter, acceleration of atrial fibrillation in preexcitation syndromes), junctional (artificial unidirectional block created by the antiarrhythmic drug which may be very effective at higher dosages: biphasic effect) or ventricular (aggravation of ventricular extrasystoles, torsades de pointe, ventricular tachycardia/fibrillation) levels. It is curious that no antiarrhythmic drug seems to be statistically less exposed to this type of complication which may result from phenomena of toxicity or idiosyncrasy. Given the potential gravity measures must be taken to prevent this complication, by observing simple rules (respect of contraindication, use of progressive dosage regimens, avoidance of loading doses, elimination of predisposing factors and abstention from dangerous therapeutic associations) and by carefully following up high risk patients.     

Ablation of atrial fibrillation: where are we now?]

Atrial fibrillation is the commonest arrhythmia. Besides the risk of complications, a significant number of patients remain symptomatic despite the different anti-arrhythmic drugs currently available. The only curative treatment is by surgery or catheter ablation. Since 1994, several approaches have been developed based on two main concepts: modification of the arrhythmogenic substrate by linear lesion to prevent the perpetuation of the arrhythmia and ablation of the foci initiating the atrial fibrillation. The later approach is the most popular one at the moment because the concentration of foci at the site of the pulmonary veins makes it possible to isolate them relatively easily. The presence of atrial foci in some patients complicates matters and limits the success rate to 70%. Despite these limitations and with an acceptable rate of complications, this approach appears preferable to His bundle ablation in young patients with symptomatic paroxysmal atrial fibrillation resistant to antiarrhythmic therapy.     

Electrophysiological remodeling induced by atrial fibrillation. An experimental curiosity or major factor in atrial fibrillation in man?

Atrial fibrillation usually progresses from a paroxysmal to a permanent arrhythmia, even in the absence of underlying cardiac disease. The treatment is more difficult when the arrhythmia is chronic. This progression may be explained by the aggravation of underlying cardiac disease with time. Another explanation is that the arrhythmia induces functional and structural changes of the atrial tissues (remodelling) which promote the perpetuation of the arrhythmia and which make treatment less effective. Although the electrophysiological changes predisposing to atrial fibrillation have been known for over 15 years, it was only in 1995 that experimental studies showed the presence of atrial electrophysiological remodelling induced by the arrhythmia. This process of long term adaptation of the atrial myocytes to the tachycardia comprises marked changes of the parameters which sustain the arrhythmia: changes in refractory period (decreased duration, inadaptation to the heart rate, increased dispersion), reduced conduction speed and sinus dysfunction. Atrial remodelling also affects the contractile function by the structural changes. The calcium currents play a major role in its development. This mechanism has not yet been completely defined in the clinical setting and its importance in sustaining the arrhythmia has not been clearly evaluated. Atrial fibrillation remains one of the most difficult arrhythmias to treat. A better understanding of cellular mechanisms of remodelling could open up new therapeutic approaches to limit the natural history of the arrhythmia with progression to chronicity and structural changes responsible for the degradation of atrial contractility.     

New concepts in understanding and modulating atrial repolarisation in patients with atrial fibrillation

Atrial fibrillation is the most frequent cardiac arrhythmia in clinical practice. Although much has been learned, the underlying mechanisms are incompletely understood. Clinically used antiarrhythmic drugs are limited in their efficacy to terminate atrial fibrillation or to maintain sinus rhythm and were associated with substantial toxicity including life-threatening ventricular arrhythmias. Novel therapeutic approaches suggest targeting of atrium-selective ion channels and pathology-specific alterations in atrial repolarisation and arrhythmogenesis as promising drug targets for patients with atrial fibrillation. This article focuses on novel aspects of altered atrial repolarisation and discusses atrium-selective (I(Kur), I(K,ACh)) and pathology-specific (I(K,ACh)) ion channels as potential targets for safe and effective treatment of atrial fibrillation.     

Atrial fibrillation: where is the border between pure antiarrhythmic and non-antiarrhythmic medicines?

The author discusses the modern approaches to the treatment of atrial fibrillation including the use of omega-3 polyunsaturated fatty acids that have antiarrhythmic properties and have favorable effect on arrhythmia substrate.     

Electrophysiologic remodeling and drug treatment of atrial fibrillation

Since 1995, a number of studies have established and detailed the mechanisms of electrical and structural atrial remodeling induced by atrial fibrillation. Atrial remodeling involves many cellular components, from ionic channels to connexins. The determination of these mechanisms may help to define a new therapeutic targets of atrial fibrillation, a frequent arrhythmia that remains difficult to treat. Atrial remodeling prevention may lead to limit the evolution of the arrhythmia (early recurrences after reduction, AF secondary to atrial tachycardia, permanent AF, decrease in atrial contractility, sinus dysfunction). Except amiodarone, the usual antiarrhythmic drugs have no effect on atrial remodeling. Calcium channel inhibitors prevent early remodeling but have no effect on prolonged remodeling. Digoxin increases remodeling. Angiotensin II receptor inhibitors have been shown to prevent early AF recurrence after reduction and are very promising in such a direction. Other methods such as the one of antioxidant therapy seem to be promising and could define soon a new antiarrhythmic therapeutic class, the antiremodeling drugs.     

Arterial hypertension and atrial fibrillation: Selecting antihypertensive therapy

Arterial hypertension is the most common cardiovascular disease. Atrial fibrillation in hypertension has frequent occurrence, which increases with age. While the mechanism underlying the development of atrial fibrillation is complex, hypertension is considered one of the main pathogenic factors resulting in this arrhythmia. Hypertension is also the key risk factor for stroke, with the risk markedly increasing in the presence of atrial fibrillation. In addition, hypertension is a major factor when stratifying the risk of thromboembolism in atrial fibrillation.Antihypertensive therapy reduces not only the risk for stroke but also the risk for atrial fibrillation.Based on current evidence (mostly retrospective data), some classes of antihypertensive agents seem to be more effective than others in preventing recent-onset atrial fibrillation. This paper discusses various options of antihypertensive strategy in hypertensive patients with atrial fibrillation. Anticoagulation and antiarrhythmic therapy make an integral part of AF management.     

Atrial fibrillation: from ion channels to bedside treatment options

Atrial fibrillation is now the most common arrhythmia in clinical practice. Recent understanding of the abnormalities in ion flow that underlie atrial fibrillation has led to the search for new treatment options with improved efficacy and tolerability. The purpose of this article is to review the role of ion channels in the development of atrial fibrillation and discuss the nature of their inhibition by investigational antiarrhythmic agents. Novel treatments include the benzofuran derivative dronedarone, atrial-selective compounds (eg, vernakalant), multichannel blocking agents (eg, tedisamil), and gap junction modifiers (eg, rotigaptide). Targeted antiarrhythmic therapies have the potential to provide safer and more effective management options for patients with atrial fibrillation.     

Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group 'Hypertension Arrhythmias and Thrombosis' of the European Society of Hypertension

Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.     

Molecular biology of the heart atrium. New insights into the pathophysiology of atrial fibrillation as well as its clinical implications

Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the most important factors for embolic stroke. In recent years, a tremendous amount has been learned about the pathophysiology and molecular biology of AF. Thus, pharmacologic interference with specific signal transduction pathways appears promising as a novel antiarrhythmic approach to maintain sinus rhythm and to prevent atrial clot formation. This review highlights the underlying molecular biology of atrial fibrillation, which may also be relevant for AF therapy.     

Le r?le des médicaments non anti-arythmiques dans la prévention de la fibrillation auriculaire

After cardioversion of atrial fibrillation, structural and electrophysiologic remodelling of the atria is implicated in the arrhythmia recurrences despite antiarrhythmic drug treatment. Strategies targeting this substrate have therefore been proposed. In this view, Renin angiotensin system inhibition and drugs targeting inflammation and oxidative injury are the most promising strategies up to now. We discuss here the rationale and evidence which are behind these therapeutic approaches.     

Effect of radiofrequency ablation of atrial flutter on the natural history of subsequent atrial arrhythmias

Introduction: Patients with atrial flutter (AFL) treated medically are at high risk for subsequent development of atrial fibrillation (AF). Whether curative radiofrequency ablation of AFL can modify the natural history of arrhythmia progression is not clear. We aimed to determine whether ablation of AFL decreases the subsequent development of AF in patients without previous AF. Methods and Results: Patients with AFL as the sole atrial arrhythmia were selected from patients who underwent successful AFL ablation at Mayo Clinic between 1997 and 2003 (N = 137). The cohort was divided by presence (n = 50) or absence (n = 87) of structural heart disease. A control group comprised 59 patients with AFL and no history of paroxysmal AF, who received only medical therapy. Occurrence of AF after AFL ablation was compared among study groups and controls. Symptomatic AF occurred in 49 patients during 5 years of follow‐up after AFL ablation, with similar frequency in both study groups. The cumulative probability of paroxysmal and chronic AF was similar in controls and each study group. By multivariate analysis, the AFL ablation procedure carries significant risk of AF occurrence during follow‐up. Fifty patients discontinued antiarrhythmic drugs after AFL ablation, and the rate of cardioversions decreased. Conclusion: Successful ablation of AFL does not improve the natural history of atrial arrhythmia progression; postablation AF is frequent. This suggests that AFL may be initiated by bursts of AF and that in the absence of AFL substrate the AF continues to progress.     

Atrial Fibrillation: Update on Ablation Strategies and Technology

Catheter ablation has become an important and widely used treatment modality for patients with symptomatic atrial fibrillation. The superior efficacy of catheter ablation over antiarrhythmic therapy has been well established. The understanding of the pathophysiology of atrial fibrillation has led to the development of catheter-based ablation techniques. The development of techniques for catheter ablation of atrial fibrillation has rapidly progressed over the last 15 years. As our knowledge of this arrhythmia expands the strategies for ablation treatment continue to evolve. New technologies aim to improve the safety, efficacy, and speed of catheter ablation for atrial fibrillation.     

Recent progress in the epidemiology of atrial fibrillation

PURPOSE OF REVIEW: Atrial fibrillation is a common arrhythmia with serious health consequences. This review explores contributions to the characterization and control of atrial fibrillation made by recent epidemiologic efforts. RECENT FINDINGS: Topics included in this review include the classification and clinical progression of atrial fibrillation, the burden atrial fibrillation places on the individual and on the health care delivery system, temporal trends in the occurrence and effect of atrial fibrillation, and novel predictors and risk factors. In light of the clinically relevant classification system used in the 2001 American College of Cardiology/American Heart Association/European Society of Cardiology Practice Guidelines for atrial fibrillation, recent estimates of pattern-specific recurrence and progression rates are described, along with insights into the incidence and prognosis of primary and secondary atrial fibrillation. Important new studies from North America and Europe quantifying the alarming health care burden and economic effect of atrial fibrillation are summarized. A discussion of several novel risk factors recently found to be associated with the development of atrial fibrillation is also included. SUMMARY: Better characterization of the predictors, natural history, and clinical course of atrial fibrillation should ultimately support improvements in prevention, clinical decision making, and patient communication. A fuller comprehension of the current and future impact of atrial fibrillation can assist in planning health care delivery from the local facility to the international arena. Finally, there is a growing recognition that unraveling the complex interplay between atrial fibrillation and other associated diseases and their common risk factors may hold promise of deep insights into the fundamental nature of cardiovascular diseases.     

The worldwide social burden of atrial fibrillation: What should be done and where do we go?

Atrial fibrillation represents the most common arrhythmia in clinical practice and is associated with poor clinical outcome. Due to the aging of the population, the number of patients with atrial fibrillation will increase approximately 2.5-fold by the year 2050. Comparison studies between rhythm control and rate control strategies in management of atrial fibrillation have been biased by the limited efficacy of antiarrhythmic drugs in keeping an actual rhythm control, while their adverse effects may offset their antiarrhythmic benefits. In patients who are candidates for anti-bradycardia pacing atrial and dual chamber pacing have been demonstrated to be superior to single chamber ventricular pacing in reducing atrial fibrillation recurrences and in preventing progression to permanent atrial fibrillation. Algorithms aimed either to prevent atrial fibrillation relapsing or to interrupt new onset tachycardias early have been demonstrated to be safe and effective, but clinical studies which investigated their impact on clinical end points showed inconsistent results. Multifunction devices capable of delivering atrial shock have been demonstrated useful in patients who were candidates for ICD implantation because of life-threatening ventricular arrhythemias. Preliminary studies suggested a potential role of these devices in selected patients with brady-tachy syndrome without prior ventricular arrhythmias. Radiofrequency catheter ablation techniques of atrial fibrillation have been increasingly used in the last years. Both pulmonary vein ablation and left atrial circumferential ablation showed encouraging clinical results with 70-80% of patients free from atrial fibrillation with or without prior ineffective antiarrhythmic drugs. In the future, strategies to deal with the huge worldwide burden of atrial fibrillation will include a wider application of non pharmacological therapies as well as a big investment in basic and clinical research. New and more effective antiarrhythmic drugs are needed. Genetic studies will deeply change understanding and therapy of atrial fibrillation.     

Hybrid Therapy in the Management of Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia. Because of the sub-optimal outcomes and associated risks of medical therapy as well as the recent advances in non-pharmacologic strategies, a multitude of combined (hybrid) algorithms have been introduced that improve efficacy of standalone therapies while maintaining a high safety profile. Antiarrhythmic administration enhances success rate of electrical cardioversion. Catheter ablation of antiarrhythmic drug-induced typical atrial flutter may prevent recurrent atrial fibrillation. Through simple ablation in the right atrium, suppression of atrial fibrillation may be achieved in patients with previously ineffective antiarrhythmic therapy. Efficacy of complex catheter ablation in the left atrium is improved with antiarrhythmic drugs. Catheter ablation followed by permanent pacemaker implantation is an effective and safe treatment option for selected patients. Additional strategies include pacing therapies such as atrial pacing with permanent pacemakers, preventive pacing algorithms, and/or implantable dual-chamber defibrillators are available. Modern hybrid strategies combining both epicardial and endocardial approaches in order to create a complex set of radiofrequency lesions in the left atrium have demonstrated a high rate of success and warrant further research. Hybrid therapy for atrial fibrillation reviews history of development of non-pharmacological treatment strategies and outlines avenues of ongoing research in this field.     

Signal-Averaged P Wave: Technique and Clinical Applications

Background Atrial fibrillation is the most common arrhythmia encountered in clinical practice. Identification of factors predisposing to atrial fibrillation may have implications for its prevention and may facilitate the detection of patients most susceptible to atrial fibrillation and its sequelae. Prolongation of P wave duration representing intra-atrial conduction delay is inadequately visualized in a standard electrocardiogram. Accurate detection, alignment, amplification and filtering of P waves during the signal averaging process permits a better analysis of the P wave and thus atrial conduction. Signal averaged P wave electrocardiography is a noninvasive technique that has permitted the evaluation of patients at risk of developing atrial fibrillation. Several studies have correlated the abnormalities in signal averaged P wave with paroxysmal atrial fibrillation, and have demonstrated its utility in independently predicting patients at risk of developing atrial fibrillation following cardiac surgery. New uses are likely to evolve as the technique is used clinically and as the methodology is standardized. A.N.E. 1999;4(4):401–407