Atrial fibrillation (AF), the chaotic and disorganized activity of the upper chambers of the heart, is the most common cardiac rhythm disturbance. It affects approximately 1% of the US population, or almost three million people. It occurs more frequently in the aged, affecting about 5% of people over 70 and as many as 10% of people over the age of 80. AF is also considered to be the leading cause of stroke in the US, leading to as many as 30% of strokes in the elderly population.
Besides being a costly arrhythmia, AF is also extremely troubling to patients and their physicians. Most people experience symptoms ranging from a relatively minor feeling of discomfort or 'doomÔÇÖ to severe frank palpitations and even syncope. As patients go in and out of AF, they present frequently to emergency rooms for control of their heart rate and/or rhythm, consuming large amounts of time and energy for treatment.
Despite having to deal with AF for many decades, the medical profession has made remarkably little progress in treating it. Currently accepted therapies with drugs and electrical cardioversion are palliative, not curative. Many patients are told to 'live withÔÇÖ their arrhythmia as nothing can be done - they are managed chronically with anti-coagulation and rate control. Patients in whom ventricular rate may be particularly difficult to control sometimes have their cardiac conducting system purposefully destroyed (artioventricular (AV) nodal ablation) and a permanent pacemaker implanted.
In comparison with pharmacologic therapy, surgical therapy for AF has been practised for the last 15 years and has enjoyed as much as a 97% cure rate with long-term follow-up. As it is practised today, however, CoxÔÇÖs Maze-III procedure remains poorly accepted due to its complexity and morbidity. Over the last few years, there has been an explosion of interest and activity in developing less invasive techniques that would be more widely accepted by patients and physicians yet that maintain the high cure rate offered by the Maze-III.
Much of the lack of progress can surely be blamed on the paucity of basic science models in which this disease is studied. Even the classification system for this disease is confusing and antiquated. It has only recently been concluded that AF is probably not one disease, but more likely two or three, depending upon the stage at which the patient presents, how long they have had the arrhythmia, and what is the predominant rhythm disturbance. Accordingly, AF has now been divided into three classes - paroxysmal, persistent, and permanent.
The main dividing point among these varieties of AF is the patientÔÇÖs predominant rhythm. Paroxysmal fibrillation is marked by the intermittence of AF. The patient suffers from self-limited episodes of AF that convert back to sinus spontaneously. These attacks may last anywhere from a few minutes to a few days. They may occur very infrequently or several times a day. With regard to natural history, paroxysmal AF is considered by most physicians to be the 'initialÔÇÖ type of AF, as patients classically present first with paroxysmal disease, and then describe a progression to the more sustained types. Of the approximately 160,000 patients newly diagnosed with AF each year, most of them will have paroxysmal disease.
Persistent fibrillation is rather similar to paroxysmal AF, except that it is marked by the tendency to remain in fibrillation unless an intervention such as cardioversion is performed, either with medications or with an electrical shock. Patients with persistent fibrillation may also have either infrequent or frequent attacks, but will always require cardioversion to restore sinus rhythm. Some patients have presented with a long history of multiple episodes of persistent AF, having had more than 20 DC cardioversions.
Prior to 1998, little was known about the atrial properties of these patients. Relatively few electrophysiological studies had been performed on paroxysmal or persistent fibrillators. What data were available indicated that the electrical properties of the atrium in these patients were only slightly abnormal, chiefly indicated by prolonged average activation times and dispersed recovery times. However, because these patients spent most of their time in sinus rhythm, it appeared that the search for an 'AF triggerÔÇÖ was most important.
In 1998, Haissaguerre and his colleagues published the first of a series of papers in which the triggers for paroxysmal AF could be found. They found that in this patient group, over 90% of the electrical impulses that initiated AF appeared in or around the pulmonary veins (PVs).Although others have reported other trigger sites, such as the superior vena cava, it still appears that the majority of AF episodes start in or around the PVs.
Over the succeeding five or six years, there has been an enormous interest in, and effort made toward, electrically separating the PVs from the remainder of the heart in order to isolate the AF trigger. This has been variably referred to as 'PV ablationÔÇÖ or 'PV isolationÔÇÖ, and typically involves creating a series of scars that block any impulse(s) originating in the PVs from propagating outward and onto the left atrium itself.
With the rapid development of radiofrequency techniques for the ablation of various cardiac arrhythmias, the electrophysiology community has tried to adapt these techniques to PV isolation. The first procedures focused on identifying a specific firing locus within a specific vein and ablating that site. Complications were many, and even short-term cures were few. As the procedures have evolved, ablations have become more 'anatomicallyÔÇÖ guided to encompass more of the left atrium and almost never travel within the cylinder of the vein itself. These more 'Maze-likeÔÇÖ procedures have had far fewer complications such as PV stenosis or perforation, and seem to have higher cure rates. However, the procedures remain quite lengthy and still do not approach the Maze-III with regard to cure rate.
Despite these problems, PV isolation remains a worthwhile goal. Further procedural and device refinement will eventually make this procedure fast, safe and reliable at curing a large number of patients with paroxysmal and persistent AF. However, there are some considerations that are quite important as we concentrate our efforts in this direction. The first is the direction of energy application. The endocardial application of a destructive energy source will always prove problematic - too shallow a lesion will not produce complete, permanent conduction block, and there will be no long-term cure. Too deep a lesion will place collateral structures at risk of injury and perforation, chiefly the esophagus and left atrium.
Therefore, it is quite likely that the best approach to cure patients with paroxysmal and persistent AF will be to perform a PV isolation procedure through an epicardial approach.This is much safer (vide supra) and likely can be performed much more quickly as direct visualization of the device location, and the lesion can be accomplished with conventional cameras and instruments.The open questions at this point in time center on which technology to use and how to obtain access to the heart in a minimally invasive manner that will be acceptable to patients and their referring physicians.
Permanent fibrillation is a rather different arrhythmia than paroxysmal or persistent. Patients with permanent fibrillation are continuously in AF and have, by definition, failed attempts to cardiovert them back to sinus rhythm. It is beginning to be understood that in these patients there have been fundamental changes in the electrical properties of the atrium.
Most of the studies performed to date on either animal models of permanent AF, on tissue taken from patients with permanent AF, or in the electrophysiology laboratory indicate that the atrium demonstrates abnormally low conduction velocities, depressed ion channel currents, and decreased refractoriness to impulse conduction. All of these alterations translate into a decrease in the wavelength of electrical conduction such that AF can be sustained in these abnormal atria whereas it cannot in normal atria.
The lack of success seen during drug therapy, therefore, is not unexpected. If one were to design a drug that would restore the wavelength of conduction to normal and thereby prevent AF, one would either restore the conduction velocity or the refractory period. There is no drug which yet addresses the former, and our only successes have been with drugs that accomplish the latter. Unfortunately, the drugs that best prolong the atrial refractory period, such as amiodarone and dofetilide, are also the ones most plagued by annoying and dangerous side-effects. Therefore, even though drug therapy may prove effective for some patients, these agents are frequently withdrawn as time goes by.
If we cannot restore the electrical properties of the atrium such that AF can no longer be sustained, then perhaps we can modify the substrate in other ways. One way would be to reduce the available area for electrical conduction to something less than can sustain the arrhythmia. Over 40 years ago, Gordon Moe proposed that a minimum square area of atrium (6.0cm2) would be necessary to sustain AF. These experimental predictions were recently confirmed in a dog model where AF was found to sustain when the wavelength of conduction dropped below 8.7cm, corresponding to a circuit area of exactly 6.0cm2.