Perspectives on the continuing evolution of therapy for atrial fibrillation

Scope of the problem

Atrial fibrillation (AF) remains the leading arrhythmia in North America, both in 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 percent of individuals in their 60s may have AF, the prevalence increases to 10 to 12 percent 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 or 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 percent of patients over the course of three to five years, although longer term data are lacking.

Drug therapy for AF

Because of stroke risk, most patients require some form of anti-thrombotic therapy in the form of aspirin, warfarin or dabigatran. Those patients with no risk factors may completely forgo anti-thrombotic therapy. Recently published guidelines suggest that therapy with aspirin alone is adequate in patients at low risk with a CHADS score less than 1. Patients with several risk factors (older than 75 years, hypertension, diabetes, prior stroke or transient ischemic attack, left ventricular dysfunction) are at higher risk, necessitating anticoagulation therapy with warfarin.

While relatively rare 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.

Establishing appropriate rate control, however, requires some assessment of rate during rest and exertion. While most guidelines recommend that resting rates during AF be less than 90 to 100 bpm, a recent large clinical trial has shown that a resting rate less than 110 bpm is adequate for rate control. During exercise, the heart rate should be maintained at less than 120 bpm.

Restoration of normal sinus rhythm may be the most effective means of rate control. A number of studies have shown the usefulness of membrane-active, anti-arrhythmic drug therapy for maintaining sinus rhythm.

Approximately 30 to 40 percent of patients treated with anti-arrhythmic therapy achieve control over the course of one year of follow-up. These data have been validated by larger comparative clinical trials. Similar results have been reported in 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.

Left atrial activation with ablation sites

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Nonpharmacologic therapy for AF

A number of observational studies have shown that AF ablation is of benefit in eliminating AF, reducing its frequency and improving patients' quality of life.

In most studies, 75 to 85 percent of patients with paroxysmal AF have been rendered free of this arrhythmia over the course of one year of observation. Even in patients with persistent or chronic AF after ablation, the incidence of the arrhythmia is significantly decreased in 10 to 20 percent.

When Mayo researchers reviewed outcomes of ablation performed at Mayo Clinic, they found (over two years of follow-up) that the response to ablation was excellent in more than 75 percent 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.

Points to remember

• Atrial fibrillation (AF) 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 with AF require some form of anti-thrombotic therapy in the form of aspirin, warfarin, or the newer direct anti-thrombin agents such as dabigatran.
• A number of observational studies have shown that ablation is of benefit in eliminating AF, reducing its frequency and improving patients' quality of life.