Introduction

Affecting more than 2 million Americans, atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice.^[1,2] It is usually a chronic, recurring disease that is associated with significant morbidity and mortality. The past few years have seen important developments in interventional technology and techniques, so that physicians can now consider 2 approaches to treatment:

High rates of success have been reported with the catheter ablation techniques, and recently the question has been raised as to whether they should be offered to patients as first-line therapy for AF.^[3,4] In this column, we will discuss the issues surrounding the different strategies for treatment of AF, with special consideration of the risks and benefits of catheter ablation, and the current role of catheter ablation in the management of patients with AF.

Pharmacologic Strategies: Rate Control vs Rhythm Control

Discussion of treatment for AF must begin with a reminder that anticoagulation for prevention of cardioembolic stroke forms the cornerstone of medical therapy for AF. From there, however, the medical literature has focused on debate as to the most appropriate strategy for treatment of AF, ie, whether the goal of treatment should be restoration and maintenance of sinus rhythm or simply rate control of AF.

Recent randomized trials comparing "rate control" vs "rhythm control" strategies for the treatment of AF in selected populations have demonstrated that a strategy directed at maintenance of sinus rhythm yields no added improvement in mortality or quality of life over that achieved with a rate control approach.^[5-7] However, there are several important limitations to these studies that restrict their generalizability to a large proportion of the population of patients with AF. All patients enrolled in these trials were considered reasonable candidates for either strategy, and the mean age in the major trials was nearly 70 years.

The patients enrolled in Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM), the largest trial comparing these strategies, had no significant change in quality of life from study onset to follow-up, regardless of treatment group or presence of sinus rhythm, suggesting that patients were minimally symptomatic from AF at baseline.^[8] The population of patients with "lone atrial fibrillation" or significant symptoms from AF was not adequately represented in these trials.

For patients who are highly symptomatic, a rate-control strategy is often not appropriate due to disabling symptoms associated with AF, even when the ventricular response is adequately controlled. In some of these patients, episodes of AF are infrequent enough that antiarrhythmic therapy is not indicated. In others, severe symptoms or recurrent episodes of sustained AF requiring direct-current cardioversion necessitate a more aggressive strategy.

Above all, these trials demonstrated the poor efficacy of our current armamentarium of antiarrhythmic medications. Even in the AFFIRM trial, in which 63% of patients in the rhythm-control group received amiodarone, only 63% of patients assigned to this arm were in sinus rhythm at the end of the study, compared with 35% in the rate-control arm. Amiodarone has been shown to be the most effective antiarrhythmic medication for the maintenance of sinus rhythm,^[9] but its use is limited by significant noncardiovascular toxicities.

In population studies, AF is associated with an increased risk of death, even after adjusting for associated comorbidities.^[10] When the AFFIRM study was analyzed on the basis of actual rhythm at follow-up, the presence of sinus rhythm was strongly associated with a decreased risk of death (hazard ratio = 0.53).^[11] The presence of sinus rhythm was a more important determinant of outcome than the use of antiarrhythmic medications in this analysis. Therefore, even in the selected population of patients enrolled in this trial, there appears to be a benefit to sinus rhythm. The limiting factor was not necessarily the rhythm-control strategy, but the inadequate tools available to restore and maintain sinus rhythm. We emphasize that it was the strategy, not the achieved rhythm, that was being tested in this trial. All studies of this issue have demonstrated superior outcomes in patients with sinus rhythm. The problem, therefore, is how to achieve it.

Sinus Rhythm and Remodeling

Pharmacologic management of AF is directed at both maintenance of sinus rhythm and prevention of electrical remodeling and fibrosis of the atria. Currently available antiarrhythmic medications have limited efficacy and significant toxicities that curtail their use. For patients with AF and no significant cardiac disease, the Vaughn-Williams class IC drugs flecainide and propafenone are often used. Although these medications are generally well tolerated, their efficacy is limited, with less than 40% of patients maintaining sinus rhythm.^[9] Other class I agents such as quinidine, disopyramide, and procainamide have similar efficacy but less favorable side-effect and toxicity profiles.

The class III agents sotalol and dofetilide can be used in a broader spectrum of patients with AF, but require hospitalization for initiation of therapy and careful monitoring due to potentially fatal QT prolongation and torsade de pointes. In addition, these agents also have limited efficacy, with less than 40% of patients free of recurrent AF after 1 year.^[12]

Amiodarone has been proven to be the most effective drug for maintenance of sinus rhythm, with 50% to 65% of patients maintaining sinus rhythm after 1 year, but it has numerous side effects involving the thyroid, liver, lung, eye, and skin that significantly limit its use.^[9,12] Given the cumulative toxicity of amiodarone, it is often not considered an appropriate choice of therapy for younger patients with a longer life expectancy. New drugs are being developed that will have greater specificity for atrial tissue, greater effectiveness, and a more favorable side-effect profile, particularly with regard to proarrhythmic complications.

A common clinical observation is that the longer the duration of AF, the greater the likelihood a patient will remain in AF and the more difficult it will be to restore sinus rhythm. AF leads to alterations in ion channels, as well as atrial tissue remodeling due to a variety of biochemical factors, including calcium overload, oxidative stress, and activation of the renin-angiotensin-aldosterone axis. Therapies directed at prevention of atrial remodeling include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antialdosterone agents, and statins. Studies of these medications in a hypertensive population and smaller studies in patients with AF have suggested that these therapies may reduce atrial remodeling and decrease the incidence of AF.^[13,14]

Nonpharmacologic Treatment

Nonpharmacologic methods for the treatment of AF include atrioventricular junction ablation with pacing, atrial pacing protocols, atrial flutter ablation with antiarrhythmic drug treatment, surgical Maze procedure, and catheter-based AF ablation.

Atrioventricular junction ablation with pacing is an effective strategy for a small number of highly symptomatic patients with AF, but it is highly invasive and creates dependence on an implanted pacemaker.^[15] It is commonly considered in patients with AF in whom neither sinus rhythm nor rate control can be achieved and in patients who already have a pacemaker for bradycardia-tachycardia syndrome. Several studies have shown improved quality of life and improvement in ventricular function with this strategy. In patients with symptomatic heart failure and permanent AF, biventricular pacing can also be useful with atrioventricular junction ablation.

Various pacing strategies, including multi-site atrial pacing, atrial antitachycardia pacing, and atrial defibrillator therapy, have been tested for the prevention and treatment of AF, but no studies have convincingly shown a significant benefit for these patients.

In patients with primary typical right atrial flutter which degenerates into AF, a "hybrid" procedure involving atrial flutter ablation and treatment with an antiarrhythmic drug may be an effective strategy. However, this population represents only a small minority of AF patients.

The surgical Maze procedure was developed nearly 2 decades ago, and clinical results have been quite good, with reported success rates of over 90% in many trials.^[16] However, the requirement for open-heart surgery has necessarily restricted this therapy to patients undergoing cardiac surgery for other indications.

Catheter Ablation

The description by Haissaguerre of focal triggers of AF originating from the pulmonary veins (PVs) led to a new approach to the treatment of AF.^[17] Elimination of these triggers was proposed as a way to prevent the development of AF. Early approaches using focal catheter ablation of ectopic foci around the PVs had limited success, and more extensive ablation in PVs was complicated by pulmonary stenosis. Over the past several years, the approach to catheter ablation of AF has become more standardized, and 2 primary techniques have been developed.

The first technique, segmental PV isolation, involves ablation around the ostium of each PV. The goal of this procedure is electrical isolation of the PVs, and ablation is performed to reach the electrophysiologic endpoint of conduction block at the left atrium-pulmonary vein border.^[18,19] The second technique, circumferential left atrial catheter ablation, involves the creation of empiric, anatomically based ablation lines. Electrical block across these lines is not generally assessed, and this technique involves longer ablation times and larger lesions.^[20,21] There is no clear consensus as to which of these approaches is superior, and each has certain advantages. Reported success rates in the literature are similar, though the largest randomized study comparing the 2 techniques reported a higher success rate with segmental PV isolation.^[21]

Recent studies of catheter-based AF ablation have reported success rates of 67% to 88% for paroxysmal AF. Success rates for persistent or permanent AF or in patients with markedly dilated atria are lower. Although the definition of "success" is controversial, since many AF patients have asymptomatic episodes, it is quite clear that a large proportion of patients benefit from this procedure. In our practice, in which we routinely perform surveillance ambulatory electrocardiogram monitoring in all patients post-ablation, we have found that 70% of patients remain free of AF after ablation.^[22]

In a large worldwide survey of centers performing AF ablation, 52% of patients who were not taking antiarrhythmic medications were asymptomatic, and another 24% were successfully treated with antiarrhythmic medications after ablation.^[23] In addition, there is a high rate of maintenance of sinus rhythm among those patients who undergo a repeat procedure.^[24]

Despite the impressive success rates achieved with AF ablation, the risks associated with this invasive procedure must be considered. The procedure is prolonged, lasting several hours in most institutions, and requires heavy sedation or general anesthesia. Major complications have been reported in 6% of patients, and can include pericardial effusion and tamponade (1.2%), stroke or transient ischemic attack (1%), PV stenosis (0.5%-1.0%), groin access complications (1%), and atrial-esophageal fistula (rare).^[23] The latter is a widely feared complication that confers a high risk for mortality, and its incidence is fortunately extremely low. Recognition of this risk has led to altered techniques, and avoidance of posterior wall ablation and visualization of the esophagus with intracardiac echo may help to prevent this complication. In addition, left atrial tachycardia has been reported to occur in 10% to 20% of patients after ablation, and the incidence is higher when the circumferential left atrial ablation technique is used.^[21,23]

Catheter Ablation as First-Line Therapy for AF

Given the low efficacy of available pharmacologic treatments of AF and the impressive success rates of AF ablation, the question has been raised as to whether this technique should be employed as first-line therapy. Most prior trials of AF ablation have enrolled patients who had failed antiarrhythmic drug therapy.

However, this question was addressed in a recent small randomized trial of ablation vs antiarrhythmic therapy in patients with symptomatic AF who had not been previously treated with antiarrhythmic medications.^[4] The segmental PV isolation technique was employed in the group treated with ablation. In the antiarrhythmic therapy group, use of amiodarone was discouraged until patients had failed 2 other drugs. Patients were followed for 1 year, and 63% of patients treated with antiarrhythmic medications had recurrent symptomatic AF compared with only 13% in the ablation group (P < .001). In addition, the ablation group had a significantly lower rate of hospital admissions and improved quality of life.

In the trial described above, AF ablation was clearly superior to antiarrhythmic drug therapy. However, there are several issues to be considered when using ablation as a first-line therapy for AF. First, the procedure is invasive and, as noted above, has well-documented risks. Many patients initially presenting with AF may be understandably unwilling to accept these risks as part of their initial treatment plan. Second, though the efficacy of antiarrhythmic therapy is far from optimal, there is still a large population of patients who can be successfully treated with medications. In patients with structurally normal hearts without coronary disease, class IC agents and class III agents (with the exception of amiodarone) can be safely prescribed if administered appropriately with adequate follow-up. Third, catheter-based AF ablation is a new technique, and while the studies report high success rates from high-volume centers, most centers currently have limited experience. Finally, the long-term follow-up of patients after ablation is limited, and given the natural history of AF, it is quite possible that the long-term success rates of this procedure will taper off significantly.

As techniques evolve over time, the success rate of this procedure may improve and the complication rate may decrease. Allowing patients to put off a procedure may enable them to benefit from these advances.

Conclusion and Recommendations

The first step in the management of patients with AF is to determine their stroke risk and need for anticoagulation according to published guidelines. The next step is to determine whether they have symptoms that warrant a strategy directed at restoration and maintenance of sinus rhythm. Our experience is that most younger patients, active patients, and those with heart failure will require an initial approach aimed at maintaining sinus rhythm. Even patients without overt palpitations or symptoms of heart failure may be found to be significantly affected by AF upon careful questioning and examination.

Once the decision is made to pursue maintenance of sinus rhythm, the first-line therapy remains a trial of antiarrhythmic medications for most patients. Depending on the patient's age and whether he or she has a history of preexisting heart disease, either a class IA, IC, or III drug is then initiated along with direct current cardioversion if indicated. The rationale for starting with a trial of antiarrhythmic therapy is that up to 40% of patients may be effectively treated with this approach, and when properly administered, there is little risk to the patient. If the patient develops recurrent AF despite receiving an adequate dose of an appropriate antiarrhythmic medication, we then begin a dialogue with the patient about further treatment options. We discuss the risks and benefits of an AF ablation procedure in detail, as well as the option of therapy with another antiarrhythmic drug. We stress to patients that AF ablation has not been shown to decrease stroke risk, and our recommendations for anticoagulation do not change after an ablation procedure. Many patients opt for another trial of antiarrhythmic therapy, and then may proceed to ablation if the second drug or even a third drug fails. Highly symptomatic patients may opt for a catheter-based procedure at this point, however.

There are some patients in whom an AF ablation procedure can be considered first-line therapy. These include patients unable or unwilling to take an antiarrhythmic medication or patients in whom the only viable option for medical therapy is amiodarone. We feel that it is reasonable to offer such patients an ablation procedure for treatment of symptomatic AF. The results of ongoing large trials of AF ablation as first-line therapy^[3] and improvements in ablation technique may elevate this procedure to the status of first-line treatment for more patients in the future. Currently, however, a stepwise approach to the treatment of AF seems most prudent for the majority of patients.

Supported by an independent educational grant from St. Jude Medical.