Pharmacological Approach for AF Management: Interview With Leonard Ganz, MD

Briefly describe some of the ACC/AHA/ESC Practice Guidelines for the management of patients with atrial fibrillation (AF).

The ACC/AHA/ESC Practice Guidelines for the management of patients with atrial fibrillation (AF) was, at the time it was published, an exhaustive review of the AF literature. Unfortunately, at the time it was published, few randomized data were available to guide AF therapy, beyond the excellent data involving anticoagulation therapy. In addition, the field has advanced significantly since the guidelines were published, particularly in the area of nonpharmacologic therapies.

What are the current pharmacological options available for AF patients?

I think the first issue to consider is the risk of stroke, and whether therapy with warfarin or aspirin is necessary. Beyond this, other therapeutic goals include improving symptoms and controlling the ventricular rate to prevent tachycardia-induced cardiomyopathy. To achieve these goals, either a rhythm control or rate control strategy may be adopted. An important lesson from the AFFIRM trial was that rate control is a very reasonable strategy. Many patients, though, remain symptomatic despite aggressive attempts at rate control, and therefore require efforts to restore and maintain sinus rhythm.

Approximately how many AF patients do you see in your lab per month? What percentage are treated with antiarrhythmic medications versus other procedures such as ablation?

The University of Pittsburgh Medical Center is a regional and national referral center for patients with AF. Our AF volume is very high, and weighted towards refractory and symptomatic patients. Even so, the majority of our patients are treated pharmacologically. At present, we reserve focal AF ablation for highly symptomatic patients, and we typically recommend attempts at pharmacologic therapy prior to considering pulmonary vein isolation procedures.

What makes Rythmol SR unique from other antiarrhythmics available today?

Rythmol SR differs from standard, immediate-release propafenone in that it is dosed twice daily, rather than three times daily. In addition to the improved compliance one expects with bid rather than tid dosing, the more constant plasma levels one sees with Rythmol SR may translate into greater efficacy than with regular propafenone, though the two agents have not been compared head-to-head in a randomized trial. An important issue that distinguishes Rythmol SR from the class III agents like sotalol and dofetilide is that Rythmol SR can typically be initiated on an outpatient basis, while sotalol and dofetilide require hospital admission.

Describe your results using Rythmol SR in your lab.

We have been quite happy with our initial experience with Rythmol SR. We frequently use it as a first-line agent in patients with symptomatic AF despite AV nodal blockade in the setting of a structurally normal heart or in mild hypertensive heart disease. We generally use Rythmol SR in association with an AV nodal blocking agent, in the event that patients have a recurrence of atrial flutter. Interestingly, though, in the RAFT Trial, the likelihood of patients presenting with atrial flutter on Rythmol SR was quite low.

Are there certain arrhythmias that Rythmol SR is best prescribed for?

We tend to use Rythmol SR in patients with structurally normal hearts or mild hypertensive heart disease (mild left ventricular hypertrophy [LVH]), who have symptomatic paroxysmal atrial fibrillation (PAF). We do not recommend Rythmol SR for patients whose primary arrhythmia is atrial flutter or supraventricular tachycardia (PSVT); in these patients, catheter ablation is generally recommended rather than class I or III antiarrhythmic drug therapy.

Why is it important to keep pharmacological options available to AF patients?

There is certainly tremendous enthusiasm for nonpharmacologic therapies, particular pulmonary vein isolation (focal AF ablation). Techniques have certainly improved, and success rates are improving. Complications certainly can occur with this invasive procedure, though, and long-term data regarding efficacy as well as complication rates are still not yet available. For these reasons, we feel that pharmacologic therapy remains the foundation of therapy in the majority of AF patients, and we have thus far not generally recommended AF ablation as initial therapy.

What advice do you have for other electrophysiologists prescribing Rythmol SR for the first time?

It is first important to make sure that Rythmol SR is an appropriate drug for a given patient. An echocardiogram to exclude left ventricular dysfunction and more than mild LVH and a functional test to exclude coronary ischemia are appropriate. Many physicians are accustomed to admitting all patients for initiation of antiarrhythmic drug therapy, and may therefore be uneasy about outpatient initiation of Rythmol SR. A reasonable strategy is to initiate the drug in outpatients, but give them an event recorder. Patients can transmit their rhythm twice daily (or even more frequently), and with any symptoms. The RAFT data regarding atrial flutter notwithstanding, I still use Rythmol SR in association with an AV nodal blocker. I tend not to increase the dose until a week or longer has gone by. This depends on the individual patient s frequency of AF episodes; the more frequent the episodes, the more quickly one can assess the efficacy of a particular dose of a particular drug. Once the patient is stabilized on a dose that appears to be effective, I will typically have the patient do an exercise stress test, to make sure there is no evidence of an exercise-induced arrhythmia or pathologic QRS widening.

What changes, if any, do you foresee in antiarrhythmic drug therapy in the future?

I am hopeful that pharmaceutical manufacturers will continue to develop new antiarrhythmic compounds. While Rythmol SR is an excellent option in patients with structurally normal or near normal hearts, it is not an appropriate agent in patients with coronary artery disease or left ventricular dysfunction. There also appears to be an effort to develop antiarrhythmic agents which specifically target atrial rather than ventricular tissue, which would obviously be preferable in AF patients.

Is there anything else you'd like to add?

As AF itself is typically not a life-threatening problem, it is important to not put patients at significant risks with our therapies. All antiarrhythmic drugs pose some risk of proarrhythmia, though the risk of IC agents, when used in the manner described in the population of patients we have discussed, is quite low. In addition, all nonpharmacologic therapies such as focal AF ablation pose a risk of complications. For these reasons, it is important to individualize therapy for each patient. Once the issue of anticoagulation is addressed, we tend to let a patient's symptoms dictate how aggressive a therapeutic approach is required.

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