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Atrial fibrillation (AF) remains the leading arrhythmia in North America, both in the numbers of patients affected and the frequency of accompanying sequelae. The prevalence continues to increase, despite progress in the treatment of contributing factors. Although 1% of individuals in their 60s may have AF, the prevalence increases to 10% to 12% in individuals older than 80 years. Currently 2.5 million Americans have AF, but with the aging population and improved cardiovascular survival, this number may increase to 5 million to 6 million by the year 2050.
In most patients, AF is initially paroxysmal; other patients, particularly those with underlying heart disease, may have more persistent or even chronic AF. Nevertheless, the previously held belief that most paroxysmal AF ultimately progresses to a chronic form has been questioned. Recent studies have suggested that progression occurs in only 20% to 40% of patients over the course of 3 to 5 years, although longer-term data are lacking.
Nevertheless, AF becomes increasingly problematic because of AF-related thromboembolic events such as:
Perhaps 15% to 30% of patients with an acute stroke have underlying AF. Patients with AF also have an increase in overall mortality risk (15% in patients without AF vs 35% in those with AF), attributable to stroke risk and comorbid conditions. In the Framingham and other studies, it has been demonstrated that this increase in mortality is attributable to AF as a risk factor, rather than simply being caused by the presence of underlying disease.
Atrial fibrillation is an increasing burden on the global health care system because of the numbers of patients affected, the impact of stroke, and the cost of both inpatient and outpatient therapy.
Because of stroke risk, most patients require some form of antithrombotic therapy in the form of aspirin or warfarin. Those patients with no risk factors may completely forgo antithrombotic therapy, while the recent ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation have suggested that therapy with aspirin alone is adequate in those at low risk with a congestive heart failure, hypertension, age, diabetes, prior stroke (CHADS) score less than 1.
Patients with several risk factors are at higher risk, necessitating anticoagulation therapy with warfarin. This recommendation is based on an extensive series of large mortality studies consistently demonstrating the benefit of antithrombotic therapy. The risk factors include:
Despite clear guidelines and extensive experience with thromboembolic events, many patients who would benefit from antithrombotic therapy do not receive it.
Many patients have a rapid ventricular response rate during AF, which is responsible for symptoms. In some cases, rapid rates may also result in tachycardia-induced cardiomyopathy. While this outcome occurs relatively uncommonly in the absence of other heart disease, the possibility of an AF contribution to ventricular dysfunction should be considered in patients who have a rapid ventricular response rate and reduced ejection fraction. As such, many patients require rate control to prevent these sequelae and improve overall quality of life. Establishing appropriate rate control, however, requires some assessment of rate during rest and exertion. Most guidelines and recent clinical trials recommend that resting rates during AF be less than 90 to 100 beats per minute, with exercise heart rates maintained at less than 110 to 120 beats per minute.
Restoration of normal sinus rhythm may be the most effective means of rate control. A number of studies over the past 30 years have also shown the usefulness of membrane-active, antiarrhythmic drug therapy for maintaining sinus rhythm. Approximately 30% to 40% of patients treated with antiarrhythmic therapy are controlled over the course of 1 year of follow-up.
These data have been validated by larger comparative clinical trials such as the AFFIRM trial. Similar results have been reported in RACE, STAF, and other studies designed to compare rate and rhythm control therapy. Although an increase in mortality may accompany AF, comparative studies examining the utility of rate vs rhythm control therapy have had disappointing results. The AFFIRM trial, for example, showed no difference in overall mortality over the course of long-term follow-up with either treatment strategy. Similarly, the RACE, PIAF, and STAF studies yielded similar findings.
Additionally, the AF-CHF trial, which involved 1376 patients with AF, also failed to demonstrate any difference in the end points of total mortality, worsening heart failure, or the composite of cardiovascular mortality, stroke, or worsening heart failure. In addition, bradycardia and rehospitalization were more common in those treated with antiarrhythmic drugs intended to maintain sinus rhythm. These findings may have been attributable to the following scenarios:
Despite the pessimism generated by these studies, the results of the recent ATHENA trial have encouraged reconsideration of drug therapy for AF. In comparing the class III antiarrhythmic agent dronedarone with placebo in more than 4500 patients, this study showed:
There were significantly lower rates of acute ischemic syndrome and stroke with dronedarone therapy when rates of proarrhythmia and heart failure were also low. These data support the potential for cancellation of benefit from drug therapy by untoward toxicities of drug interventions, although the control rate with this drug is less than that of amiodarone.
The escalation of AF occurrence, the efficacy limitations of drug therapy, and the adverse effects and toxicity from drug therapy have provided the incentive for the continued implementation of nonpharmacologic therapy over the last decade. Atrial fibrillation ablation has been shown in a number of observational studies to be of benefit in eliminating AF, reducing its frequency, and improving patients' quality of life.
In most studies, 75% to 85% of patients with paroxysmal AF have been rendered free of this arrhythmia over the course of 1 year of observation. In patients with persistent or chronic AF and those with underlying disease, AF is decreased in 10% to 20% of patients. After longer-term follow-up, the ablation of patients with more advanced underlying disease, and a more critical view of treatment benefit without additional antiarrhythmic drugs or repeat ablative intervention, these overall success rates are lower than the more optimistic values touted in the first part of this decade.
Map of left atrial activation with ablation sites
Douglas L. Packer, M.D., director of the Heart Rhythm Center and the 2010-2011 president of the Heart Rhythm Society, reviewed outcomes of ablation at Mayo Clinic. He found that over 2 years of long-term follow-up, the response to ablation was excellent in more than 75% of patients with paroxysmal AF. Patients with persistent and chronic AF likewise have shown enhanced benefit, although a more aggressive ablative approach has been required. In those with paroxysmal AF, ablation for the isolation of pulmonary veins may be sufficient, while wider-area circumferential ablation with additional linear ablation or energy delivery directed at the underlying substrate has been required.
Additional review demonstrated notable benefit in patients with underlying dilated cardiomyopathies. In many patients, not only was AF eliminated, but a substantial improvement in ejection fraction was observed, particularly in those with nonischemic left ventricular dysfunction.
Several recent studies have gone beyond observational reports to compare the efficacy of ablative vs drug therapy in patients with paroxysmal AF. The CACAF, RAAFT, APAF, and A4 trials demonstrated a 76% recurrence rate in patients treated with drug therapy vs 24% recurrence in those treated with ablative intervention. These studies were limited, however, because of shorter-term follow-up and the exclusion of patients with underlying disease or advancing age. The impact of ablative therapy on the overall cost of health care is less certain.
Even in the absence of cost data, there is sufficient information from observational studies, meta-analyses, and comparative studies to support more widespread application of AF ablation in patients failing a single antiarrhythmic drug because of AF recurrence or intolerability.
The Guidelines for the Management of Patients With Atrial Fibrillation, endorsed by the American Heart Association (AHA) and the American College of Cardiology (ACC), recommend this nonpharmacologic approach as second line therapy. Similarly, the Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-up, developed by the Heart Rhythm Society and endorsed by the AHA and ACC, comes to a similar conclusion. A number of centers are moving toward a primary therapy role for ablation, as success rates increase and complication rates decline.
In clinical practice, it is important to be clear on the indication for any intervention in AF patients. Of primary importance is the need to prevent stoke or other peripheral thromboembolic events. Warfarin therapy has been best demonstrated to reduce this risk.
Additional studies will be required to establish a benefit in this area with membrane-active drug therapy or ablation. The role of therapy to establish and maintain sinus rhythm in patients with left ventricular dysfunction is acceptably clear-cut in recent ablation studies. Of greatest importance is the need to reduce or eliminate AF in symptomatic patients, which remains the primary indication for ablative intervention.
Patients who have failed to respond to 1 drug may be good candidates for intervention, although the anticipated success rate depends on the type of AF and the presence of underlying left ventricular or left atrial dysfunction. Age appears to be a less important issue than previously thought. Patients with underlying valvular heart disease and hypertrophic cardiomyopathy have excellent short-term outcomes although much more aggressive procedures are required.
Since 1997, more than 2500 pulmonary vein isolation procedures for the treatment of AF have been performed at Mayo Clinic. In the most recent review:
While observational studies and limited randomized comparisons demonstrate symptomatic improvement in patients undergoing ablation and early data suggest a cost benefit, larger long-term studies are required to establish a mortality benefit and a reduction in stroke risk.
As a result, the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial was designed. This study, originating from Mayo Clinic, will examine the benefit of ablation vs drug therapy in 3000 patients with AF enrolled in 140 centers around the world. Mayo Clinic recently received $48 million in grants from the National Institutes of Health and from industry to lead this collaborative effort.
The study will also establish long-term complications of AF treatment and their prevention by appropriate ablative or drug therapy. Importantly, this study will also establish the actual impact of the arrhythmia and its treatment on a patient's quality of life and health care costs.
Until these studies are completed, the application of ablative intervention will continue to be guided by a decade of observational studies and smaller randomized clinical trials, as well as information coming from national and international ablation registries.
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