New Developments in Atrial Fibrillation

Login or register to view PDF.
Citation
US Cardiology 2004;2004:1(1):110-111

Atrial fibrillation (AF) is the most common sustained, medically significant, and troublesome arrhythmia encountered in clinical practice. AF has been associated with decreased quality of life (symptoms), serious morbidity (thromboemboli and tachycardia-induced cardiomyopathy), and increased risk of mortality. Several articles have reviewed this arrthymia in depth including its presentations, prognosis and management. This review will focus on new developments in the management of AF.

When a patient presents with AF, four issues must be routinely addressed. First, is there is an underlying etiology that will be self-terminating or correctable? In these cases, AF itself is not likely to become a chronic or recurring disorder. Such etiologies include pneumonia, pericarditis, thyrotoxicosis, and thoracic surgery. In the absence of such correctable or limited entities, AF is likely to recur and thus become an on-going disorder requiring significant attention over the course of time. AF may then present in paroxysmal, persistent, or permanent forms.

The second issue is ventricular rate control. In the absence of intrinsic atrioventricular (AV) nodal dysfunction, the ventricular rate during AF will be rapid, as a result of the ultrarapid (>400-600 beats per minute (bpm)) atrial rates. Control (restoration of physiologic rates) of the ventricular response is essential both for symptom reduction and to prevent the development of a tachycardia-induced dilated cardiomyopathy (which may occur with chronic rates of 90-100bpm or higher). Control is usually achieved with the administration of one or more AV nodal depressant drugs, such as a ├ş-blocker, verapamil, diltiazem, or digitalis. There are guidelines on their relative efficacies and the factors that should underlie the specific selection in a given patient. Efficacy in each patient is best determined with a 24-hour ambulatory electrocardiograph (ECG) recorder so that the average heart rate is <90bpm, the peak ventricular rate is no greater than would be present during the same level of activity if normal sinus rhythm (NSR) were present, and the minimum rate is not excessively slow. When pharmacotherapy fails to provide adequate ventricular rate control because of either drug inefficacy or intolerance, AV node ablation and implantation of a modern rate-responsive pacemaker become the therapy of choice. Thus, rate control can be achieved in 100% of patients and is essential.

Anticoagulation is the third issue. Whether patients have paroxysmal atrial fibrillation (PAF), persistent AF awaiting cardioversion, or permanent AF, considerations regarding anticoagulation must be addressed. A simplified view of current guidelines would state that the presence of recognized risk factors that indicate an increased risk for an embolic event dictate the administration of warfarin (to an international normalized ratio (INR) value of 2.0-3.0), whereas the absence of such risk factors does not, and usually results in the use of aspirin 325mg per day.

Such risk markers include age >65 years, prior emboli, hypertension, diabetes, ventricular failure, rheumatic disease, and selected echocardiographic identifiers that may be useful in particular circumstances. When any of these risk markers is present, clinical trials have shown a greater efficacy and risk-benefit ratio for warfarin than for aspirin.

Fourth, and finally, is the issue of whether and when to pursue the return and maintenance of NSR, rather than to allow the patient to remain in AF, even if rate-controlled and adequately anticoagulated. Clearly, if the patient continues to have symptoms from AF and a less than desirable quality of life (QOL) despite rate control, sinus rhythm must be considered. For persistent AF, cardioversion would be applied and then, as with PAF, the maintenance of NSR would be sought, initially with the use of an antiarrhythmic drug (AAD).The selection of the AAD to be employed should be guided by the now internationally developed guidelines recommended jointly by the American College of Cardiology (ACC), the American Heart Association (AHA), the European Society of Cardiology (ESC), and the North American Society of Pacing and Electrophysiology (NASPE) in October 2001.

While each of the four issues regarding AF detailed previously are well recognized and reviewed, each of them has been influenced by newer or developing forms of therapy and/or by recent clinical trial data indicating that certain additional considerations regarding these four issues now require attention.

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 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.

The term 'focal triggersÔÇÖ 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. 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.

This article has been reprinted with permission: Reiffel, J A, New Developments in Atrial Fibrillation:, Cardiology Special Edition,Volume 9, number 1, 2003.