Underlying Etiology

In the past, correction of underlying etiology focused on an associated disorder that initiated or contributed to maintaining the presence of AF. In recent years, the focus has shifted, aspects of the heart itself are beginning to be targeted, with the intention of curing AF. In this respect, two broad areas of atrial electrophysiology require attention – remodeling and focal initiators.

Remodeling(4) is a term that has been applied to the changes that occur in the atrium as a result of persistently rapid rates (whether iatrogenic, as with rapid pacing experiments, or spontaneous, as with atrial tachyarrhythmias). Rapid rates in the atrium in themselves lead to shortening of atrial refractory periods, dilation of the atrium, and alterations in atrial metabolic characteristics (the constellation of remodeling), which allow a greater number of re-entrant wavelets to form and persist and which thereby increase the ability of AF to be maintained. As such, AF begets AF. Several investigative examinations have suggested that remodeling is, at least in part, a product of calcium overload and may be reduced or prevented by the administration of a calcium channel blocker (most of the work has been done with verapamil) before or shortly after the initiation of AF. Thus, while verapamil itself is not an agent that will cause cardioversion of AF back to normal or will be useful in the long-term as an antiarrhythmic drug (AAD) to prevent recurrent AF, verapamil has been shown to reduce early recurrence of AF after cardioversion and to prevent the atrial remodeling effects of recent AF. It may facilitate other AADs in this circumstance and may be the first-choice agent for rate control of recentonset AF, in the absence of a contraindication. (5)

The term ‘focal triggers’ refers to the finding that, in many patients, particularly those with very frequent episodes of PAF and no associated structural heart disease,AF appears to be initiated by localized (focal) atrial foci that fire repetitively and often rapidly – conduction from these foci breaks down in the atrial tissue and results in AF. In most of these patients, the foci have been located in one or more of the pulmonary veins, where bands of atrial muscle extend several centimeters into and/or around the mouth of the veins. In some patients, similar findings have occurred in other atrial venous inflow structures, such as the Venae cavae.When such regions are identified, ablative energy, applied to eliminate the trigger or to isolate electrically the source from the body of the atrium, has been effective in preventing further AF episodes and may be viewed as a cure. Unfortunately, there is not yet uniformity to the methodologic approach – the available techniques and equipment still require long, often multiple repeated procedures, are laboratory-dependent, and carry significant risk.They may be best viewed as still investigational, although they are carried out routinely in some laboratories worldwide. Because of the complexity of the procedure and the risks (including pulmonary vein stenosis with chronic pulmonary hypertension, cardiac perforation, emboli, and death), patients in most laboratories are usually selected from those with highly symptomatic, drug-resistant AF, and the procedure should not yet be considered a first-line therapy.As an outgrowth of this approach, catheter ablation techniques are being developed for more diffuse atrial lesions in hopes of achieving a cure for permanent as well as paroxysmal AF. Candidates for focal ablation are best characterized by minimal or no structural heart disease, frequent symptomatic PAF despite rate control, and repeated bursts every day during Holter monitoring. Because these patients have failed to respond to at least two types of antiarrhythmic drugs, they are willing to accept the procedural risks, a high likelihood of repeated procedures, and only a modest success rate.

The catheter ablation approach to AF grew out of the surgical approach to AF, known as the Cox-Maze procedure.6 In this procedure and its subsequent modifications, the right and left atria are sectioned into maze-like channels so that sustained re-entrant loops supporting AF cannot be maintained. Using modern surgical methods, New York-Presbyterian Hospital in New York City, and other centers are now modifying this technique so that it mimics the focal approach to catheter ablation in many respects.

Limited surgical lesions, created by radiofrequency, cryoablation, and/or incisions, can be applied to target areas, around the pulmonary veins for example, via a thoracoscopic approach (sometimes robotically) without an open chest procedure and with very short postsurgical hospital stays. The New York-Presbyterian Hospital is comparing the different approaches and analyzing which has the highest efficacy and safety profile as initial therapy. Some patients obtain the best results with a combination of the surgical and catheter approaches.The hospital has used the surgical approach in combination with other cardiac surgical procedures, such as valve replacement, but also as an independent procedure in patients who require an AF cure for situational purposes, such as a commercial airline pilot.

Ventricular Rate Control

As previously indicated, ventricular rate control is required in all patients with AF and can be achieved in all patients if both drug and nonpharmacologic approaches are thoroughly explored. Also, as indicated above, recent data support the use of verapamil as the initial rate control drug for new-onset AF unless the underlying etiology, such as post-MI, would strongly favor an alternative agent, or unless comorbid disease or therapy prevents its use.For example, the use of dofetilide (Tikosyn, Pfizer) as an AAD precludes the use of verapamil, and indicates caution if diltiazem is employed. Also new in the realm of rate control is the appreciation of the fact that most patients with AF have both symptomatic and asymptomatic periods/episodes(7) and that, in general, the asymptomatic episodes have slower ventricular rates than the rates found in symptomatic episodes. Thus, the absence of AF symptoms does not provide proof positive of the absence of recurrent AF episodes, especially in patients with documented rate control. Accordingly, one cannot use the history of an absence of symptoms to assure the absence of AF episodes.Thus, one cannot use such a history to decide when or whether to discontinue the use of an anticoagulant regimen.Accordingly,memory-loop event recorders have been modified not only to allow patienttriggering for evaluation of appropriate symptoms, but also to auto-trigger for periods of AF.These recorders are currently available from commercial sources but do not appear to be used yet with an appropriate frequency as a guide to control of total AF burden. In patients who not only have AF but also have an indwelling device (pacemaker or defibrillator) for a concomitant cardiac dysrhythmia, interrogation of the device may also allow recognition of periods of AF that may not have been recognized by the patient.This should be a routine part of the follow up protocol for patients with such devices.